Heme/Onc Exam 1 Cards Flashcards
Polycythemia
Increase in the total amount of Red Blood Cells, amount of Hb and RBC mass in circulation
Anemia
Reduction in the total number of red blood cells, Amount of Hb or RBC mass in circulation
Anisocytosis as defined by RDW
Variation in RBC size indicated by an RDW > 14.5
Poikilocytosis
Variation in RBC shape
Poikilocytosis
Variation in RBC shape
Polychromasia
Increase in blood reticulocyte count due to their premature release
Hypochromia
Central pallor greater than 1/3rd of the RBC
Microcytosis
Abnormally small RBCs
Macrocytosis
Abnormally large RBCs
Acanthocyte
Irregularly Spiculated RBC
Echinocyte
RBCs with short regular spicules such as in uremia
Spherocyte
RBC without central pallor
Spherocyte
RBC without central pallor
Ovalocyte
Elliptical RBC
Schistocyte
Fragmented bi or tri polar spiculated cell
Sickle cell
Bipolar spiculated RBC
Stomatocyte
Mouth like deformity
Target cell
RBC with concentric circles such as in thalassemia
Tear Drop
Unipolar spiculated RBC such as in myelofibrosis
Amount of blood in a healthy male/female
12 pints male, 9 pints female
Amount of blood in a healthy male/female
12 pints male, 9 pints female
5 Functions of Blood
Transport for Oxygen and nutrients
Blood Loss prevention
Immune response to fight infection
Carries waste to Kidney and Liver
Body temperature regulation
Lifespan of a RBC
120 days
5 types of WBCs
Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil
Most abundant White Blood Cell
Neutrophill
What stimulates platelet production and where is it released from?
Thrombopoietin from the liver and kidney
Where are extra platelets stored
In the spleen
Platelet lifespan
7-10 days
Fishbone documentation for CBC from top clockwise
Hgb, PLT, HCT, WBC
Normal RBC range for Males and Females
4-6 x 10^6 for males
3.5-5 x 10^6 for females
Erythrocytosis
Increased RBCs
Erythrocytopenia
Decreased RBCs
Normal Hgb for males and females
14-17.5 for Males
12-16 for females
Equation for calculating hematocrit
(RBCxMCV)/10
Normal hct ranges for males and females
39-49% for males
35-45% for females
Equation for calculating hematocrit based on hemoglobin
Hgbx3
Mean corpuscular volume
Reflects the individual size of red blood cells
Normal MCV
80-100 fL
Mean corpuscular hemoglobin
Weight of hemoglobin per RBC
Normal range for MCH
27-33 pg
Low, normal and high MCH
Hypochromia, normochromia, Hyperchromia
Calculation for MCH
(Hgb/RBC) x 10
Mean corpuscular hemoglobin concentration
Average hgb concentration per RBC
Normal MCHC level
31-36%
Equation for MCHC
Hgb/Hct
Red Cell Distribution Width (RDW)
Measures percent of RBCs that fall outside of the normal distribution range
Normal RDW range
11.5-14.5
Normal platelet range
150-450 x 10^3 mcL
3 variables to adjust for in hematocrit
Age, Altitude, Ethnicity
Normal Mean Platelet Volume Range (MPV)
7.5-11.5
Relation of MPV and platelet production
Young platelets are larger than older platelets so a higher MPV indicates increase in the production of platelets
When can a peripheral blood smear be better than a machine blood count
When coagulation of a sample and clumping of platelets leads to false thrombocytopenia
4 Steps in erythropoiesis
Low oxygen delivery -> EPO stimulation -> RBC proliferation and maturation -> Reticulocyte release
Role of EPO in RBC maturation
Binds to proerythroblasts inducing cell maturation
Roles of folate and B12 in RBC maturation
Assist in proliferation of early to late erythroblasts
Role of Iron in RBC maturation
Assists in the accumulation of hemoglobin leading to the normoblast and then reticulocyte stages
3 defining characteristics of a reticulocyte
Not biconcave, Blue in color, May contain RNA
Lifespan of reticulocytes
Total of 4-5 days
3 days in Bone marrow
1-2 days in the blood
Normal reticulocyte count range
.5-1.5%
Technical definition of anemia
Reduction in one or more of the major RBC measurements Hgb, HCT, or RBC
Kinetic approach to anemia
Addresses the mechanism responsible for the fall in hemoglobin concentration
Morphologic approach to anemia
Categorizes anemias based on alterations in RBC characteristics and the reticulocyte response
3 mechanistic causes of anemia
Decreased RBC production
Increased RBC destruction
Blood Loss
Daily average RBC turnover
1% per day
5 common causes of reduced RBC production
Lack of nutrients
Bone marrow disorders
Bone marrow suppression
Low levels of trophic hormones
Acute/chronic inflammation
3 Causes of increased RBC destruction
Inherited hemolytic anemias
Acquired hemolytic anemias (ie. autoimmune)
Hypersplenism
4 types of blood loss
Gross blood loss
Occult blood loss
Iatrogenic blood loss
Underappreciated menstrual blood loss
Anemia is a _____________________ not a ____________________
Anemia is a symptom not a disease
How does blood loss compound anemia issues
Because blood loss leads to a lack of iron which makes it hard to then form replacement RBCs
Size of reticulocytes compared with normal RBCs
Reticulocytes are larger than normal RBCs
4 Causes of Macrocytic anemia
Folate or B12 deficiency, Drugs that interfere with nucleic acid synthesis, Abnormal RBC maturation, Alcohol abuse or liver disease
2 Causes of Microcytic anemia
Iron deficiency or Thalassemia
3 causes of normocytic anemia
CKD, Anemia of inflammation, Mild iatrogenic anemia (ie. too many blood draws
Symptoms of anemia are generally related to what?
Decrease in oxygen delivery to the tissues, and hypovolemia secondary to blood loss
Oxygen extraction compensation for anemia
Adequate when Hgb is greater than 8-9g/dL percent of O2 extracted from hemoglobin can rise from 25% to 60%
Heart compensation for anemia
How low can it go?
Increase in SV and HR adequate until Hgb falls below 5 g/dL
4 Questions to ask when presented with an anemic patient
Is the patient bleeding?
Is there evidence of RBC destruction?
Is there bone marrow destruction?
Is there a nutritional deficiency of Iron, Folate, or B12?
DD for new versus life-long anemia
New is likely acquired while life-long is more likely genetic
6 associated symptoms of anemia
Melena, Hematochezia, Menorrhagia, Renal failure, Rheumatoid arthritis, CHF
4 Skin signs that are relevant to anemia
Pallor, Jaundice, Petechiae, Bruising
2 non-blood sources of tarry stools`
Pepto Bismol and Iron supplements
4 places to check in an anemia related physical exam
Lymph nodes, Abdomen for Hepatosplenomegaly, Bony tenderness, Stool for occult blood
Two things that could make RBC and H&H low
Decreased RCM (Red Cell Mass) or Increased Plasma Volume
One thing that could make RBC and H&H elevated
Decreased plasma volume
Affect of blood loss on CBC readings - early vs. late stages
Does not show initially because equal amount of RBCs and plasma are lost, shows later when fluid is regained and dilutes blood
Problem with reticulocyte count in anemic patient
Lack of RBCs may falsely increase percentage of reticulocytes
Reticulocyte index calculation
%Reticulocytes x (Pt HCT/Normal HCT)
What does haptoglobin do?
Binds free hemoglobin that is released from RBCs
3 Markers of hemolytic anemia
Increased serum Lactate dehydrogenase (LDH) Increased unconjugated bilirubin, Decreased serum haptoglobin
Coombs test
Test for presence of antibodies of RBCs, a positive test indicates an autoimmune hemolytic anemia
Why is an automatic blood counting mechanism preffered?
A larger volume of blood can be sampled
3 Ways the body looses iron
Perspiration, Loss of epithelial cells, Menstruation
Distribution of iron in the body
65% in hemoglobin, 30% stored in the spleen or bone bone marrow, 4% in myoglobin
Normal serum iron values for Men and Women
65-175 mg/dL for men, 50-170 mg/dL for women
Normal percentage of bound transferrin
10-50%
Ferroportin, Transferin, Ferritin, Hepcidin functions
Ferroportin helps iron LEAVE cells, Transferrin transports Iron AROUND the body, Ferritin STORES iron in the body, Hepcidin BLOCKS ferroportin to decrease iron uptake
What 2 lab values make men or women anemic
Hemoglobin less than 12 for females and less than 13.6 for males
Hematocrit less than 36% for females and less than 41% for males
Intravascular hemolytic anemia
RBCs lyse within blood vessels
Consequences of intravascular hemolytic anemia (3)
Hgb is released into circulation decreasing haptoglobin, Total body iron decreases, Schistocytes form
Extravascular hemolytic anemia
RBCs are destroyed within the spleen and liver
Consequences of extravascular hemolytic anemia
Iron DOES NOT decrease, Sphereocytes are formed, Haptoglobin may not increase
Cause and epidemiology of Hereditary spherocytosis
Genetic defect that is often Autosomal dominant and results in the malformation of RBC proteins. Affects 1 in 5000 northern europeans
Pathology or hereditary spherocytosis
RBCs are round rather than biconcave, they become stuck in red pulp of the spleen and get destroyed
Presentation of hereditary spherocytosis
Jaundice, enlarged spleen, possible gallstones, RBCs with a lack of central pallor
Lab values for hereditary spherocytosis
H/H
Reticulocytes
MCHC
MCV
Haptoglobin
Peripheral smear
Coombs
H/H - Decreased
Reticulocytes - Increased
MCHC - May be elevated
MCV - Normal or Low
Haptoglobin - Normal or mildly decreased
Peripheral smear - Shows sphereocytes
Coombs - Negative
Transfusion recommendations for extravascular hemolytic anemias
NOT recommended unless anemia is very severe because it will lead to excessive iron in the body, EPO is a better option
3 Non definitive treatments for Hereditary spherocytosis
Folic acid, Transfusion or EPO for SEVERE cases
Definitive treatment for Hereditary Spherocytosis
Splenectomy preferably after 5 years of age or puberty in moderate cases
May observe if mild
Ant pneumococcal vaccination
Composition and abundance of the three hemoglobins
Hemoglobin A:
2 alphas 2 betas 97-99%
Hemoglobin A2:
2 alphas 2 deltas 1-3%
Hemoglobin F: - Fetal Hemoglobin
2 alphas 2 gammas less than 1%
Location and copies of the alpha globulin gene
Chromosome 16, 2 copies for 4 total genes
Location and copies of the beta globulin gene
Chromosome 11, 1 copy for 2 total genes
Cause of Alpha Thalassemia
Gene deletions result in reduced alpha chain synthesis
Pathology of alpha thalassemia (4)
Increase in small, pale RBCs, excess beta chains precipitate, RBC membranes are damaged, hemolysis occurs in the spleen and bone marrow
Common demographic for alpha thalassemia
Southeast Asian and Chinese descent, may be seen in mediterranean or African patients
The five degrees of alpha Thalassemia
4 working genes = Normal
3 working genes = Minima/Silent carrier, normal levels
2 working genes = Alpha thalassemia minor, HCT 28-40% MCV 60-75
1 working gene = Hemoglobin H disease, hemoglobin H is made of 4 beta chains and is barely useful HCT 22-32% MCV 60-70
0 working genes = Hydrops fetalis, die in utero late second to early third trimester
Alpha thalassemia lab findings
H/H
RBC
MCV
Reticulocytes
MCH
Hemoglobin Electrophoresis
Peripheral Smear
H/H - Normal or decreased
RBC - Increased
MCV - Markedly decreased
Reticulocytes - Normal or Increased
MCH - Decreased
Hemoglobin Electrophoresis - Normal in silent carriers and thalassemia minor, HbH bands with HbH disease
Peripheral Smear - Inclusion bodies in HbH disease, hypochromic, microcytic with target cells
Hemoglobin H disease smear presentation (3)
Hypochromic microcytic cells, Target cells, Poikilocytosis
Treatment for Alpha thalassemia Minima and Alpha thalassemia Minor
Genetic counseling only for Minima
Genetic counseling and possible transfusions or iron chelation in Minor
Treatment for Hemoglobin H disease
Two things to avoid
1 thing to monitor
And two potential treatments
Avoid iron and oxidative drugs, Monitor for iron overload and transfuse when necessary. May consider splenectomy in severe conditions
Treatment for hydrops fetalis
In utero transfusions are not recommended, Termination of pregnancy often recommended due to maternal morbidity
3 beta chain alleles
Beta - Normal production
Beta+ - reduced production
Beta0 - Absent production
Hb electrophoresis of beta thalassemia
Increased proportions of HbA2 and HbF
Demographics of beta thalassemia
Most common in Mediterranean descent patients may be seen in African or Asian patients as well
Pathology of beta thalassemia (4)
Many small pale RBCs (microcytic, hypochromic anemia), hemolysis in marrow spleen and liver, alpha chain inclusion bodies damaged erythroid precursors and surviving RBCs have a shortened lifespan
Intra and extra medullary fates of RBCs in beta thalassemia
Intra - Premature death via apoptosis
Extra - Shortened RBC survival
Genotypes for beta thalassemia minor
beta/beta+
beta/beta0
Needs of beta thalassemia minor
No transfusions needed
Hematocrit of beta thalassemia minor
28-40% 80-95% HbA 4-8%HbA2 1-5%HbF
Allele of beta thalassemia intermedia
beta+/beta+
Needs of beta thalassemia intermedia
Occasional blood transfusion
Hematocrit of beta thalassemia intermedia
Overall, A2, A, F
17-33% 0-30%HbA 0-10%HbA2 6-100% HbF
Alleles of severe beta thalassemia (major)
Beta0/beta+
beta0/beta0
Hematocrit of beta thalassemia major
may be less than 10%
Lab findings for beta thalassemia
H/H
RBC
MCV
Reticulocytes
MCH
Electrophoresis
H/H - decreased
RBC - increased
MCV - markedly decreased
Reticulocytes - normal or increased
MCH - decreased
Hemoglobin electrophoresis - Abnormal proportions (less HbA)
What would I observe in a beta thalassemia minor smear?
Hypochromic microcytic cells and target cells
What would I observe in a beta thalassemia intermedia smear?
Hypochromic microcytic cells and target cells, Poikilocytosis
What would I observe in a beta thalassemia major smear?
Hypochromic microcytic cells and target cells, Poikilocytosis, Nucleated RBCs
Facial phenotype of beta thalassemia
Chipmunk Facies
Treatment for beta thalassemia minor
Mostly just genetic counseling, monitor for iron overload
Treatment for beta thalassemia intermedia
Genetic counseling, transfusions or splenectomy may be needed. monitor for iron overload
Treatment of beta thalassemia major (4)
Monitor for iron overload and avoid iron supplements
Splenectomy of frequent transfusions
Luspatercept indicated fortransfusion dependant adults
Bone marrow transplant - definitive
MOA for Luspatercept
Promotes production of RBCs in beta thalassemia patients by interfering with TGF-beta signaling
Sickle cell and its cause
Autosomal recessive inherited disease
Hb-S composed of two alpha chains and 2 beta-s chains
Demographics of sickle cell anemia
1 in 400 black children in the US
Pathology of sickle cell disease
Polymerized HbS causes sickle shapes which gets stuck in capillaries causing ischemia and pain
Episodes can be triggered by various stressors like acidosis or anxiety
Hematocrit of sickle cell disease
20-30%
Lab findings for sickle cell disease
H/H
MCV
Reticulocytes
WBC
Electrophoresis
H/H - Normal with trait, low with anemia
MCV - normal
Reticulocytes - increased 10-25%
WBC - Elevated12000-15000
Electrophoresis - HbS band present
Peripheral smear findings for Sickle cell anemia (3)
Target cells, Sickled RBCs, Howell Jolly inclusion bodies
5 symptoms of Sickle Cell Anemia
Poorly healing ulcers of LE, Sausage fingers and toes, Retinopathy, Splenomegaly, Cardiomegaly
Clinical manifestation of a sickle cell crisis
Sudden pain, hand/feet pain less than 18 months, long bone pain children/teens, vertebral pain adults, Fever and tenderness
Items of note in a sickle cell retinal exam
hemorrhages, white cotton spots, tortuous veins
Splenic size in sickle cell anemia
grows until about 3 years old and then shrivels
Onset of sickle cell anemia
about 6 months
3 suggestions for sickle cell treatment
Low impact exercise, Medicate ANY fever, avoid stress
Common medication for sickle cell anemia treatment
Hydroxyurea - increases HbF levels and suppresses immune system, teratogenic!
Sickle cell alternative to hydroxyurea
L-glutamine (pharm grade)
Other potential drug for sickle cell disease
Crizanlizumab - reduces interaction of RBCs with the endothelium also used in patients who cannot tolerate hydroxyurea
Definitive treatment for sickle cell anemia
Stem cell transplantation
HOP treatment for acute sickle cell crisis
Hydration, Oxygenation, Pain control
Splenic sequestration crisis
Disproportionate amount of blood sequestered in spleen, HgB drop of 2 g/dL below baseline
Inheritance/MOA of G6PD deficiency
X-linked recessive genetic defect resulting in a deficit of the glucose-6-phosphate dehydrogenase enzyme
Demographic for G6PD deficiency
Most common in African american males although it can also be seen in patients of Asian and mediterranean descent
Pathology of G6PD deficiency (how it works)
Makes RBCs especially vulnerable to oxidative stress causing Hb to denature and form precipitate (Heinz bodies). Cells are destroyed by the spleen or rupture spontaneously
Presentation of G6PD deficiency
Usually asymptomatic with episodes of hemolytic anemia, no splenomegaly and potential prolonged jaundice in newborns
3 major triggers for G6PD deficiency
Antibiotics (sulfas, quinolones, nitrofurantoin); Aspirin or Phenazopyridine; Food (FAVA BEANS, soy, red wine, blueberries)
Lab findings for G6PD deficiency
H/H
MCV
Reticulocytes
MCH
G6PD Assay
H/H - Normal between episodes; low during episodes
MCV - Normal
Reticulocytes - Increased during episodes
MCH - Normal
G6PD Assay - Decreased, may be normal during episodes
Presentation of G6PD patient during an episode - 5 symptoms
Malaise, Weakness, Abdominal or Lumbar pain, Jaundice, Dark urine
4 peripheral smear findings for G6PD deficiency
Bite cells, Blister cells, Polychromatophils/reticulocytes, Heinz bodies seen when stained
3 Preventative measures and 2 therapeutic measures for G6PD deficiency
Preventative:
Avoidance of oxidant drugs
Avoidance of trigger foods
Genetic counseling
Therapeutic measures:
Removal of offending agent
Folic acid supplementation
Presentation of autoimmune hemolytic anemia
Abrupt, rapid onset, life threatening anemia - may be confused with drug induced hemolytic anemia
Pathology of autoimmune hemolytic anemia
RBCs are tagged for destruction, become spherecytes in the spleen and are stuck. RBCs are also destroyed by Complement and MAC in the liver and intravascular setting
Warm autoimmune hemolytic anemia
Autoimmune hemolytic anemia that happens at regular temperatures and is more common
Cold autoimmune hemolytic anemia
Autoimmune hemolytic anemia that is activated at colder temperatures, invloves cold agglutinins
Lab findings for Autoimmune hemolytic anemia
H/H
RBC
MCV
Reticulocytes
MCH
Platelets
H/H - Decreased (can drop fast)
RBC - Decreased
MCV - normal
Reticulocytes - increased
MCH - normal
Platelets - 10% have thrombocytopenia
Direct and Indirect Coomb’s test method and meaning
Direct - Reagent mixed with pt RBCs agglutination means that Ig and complement are on the RBC surface
Indirect - Pt serum is mixed with Type O or donor RBCs and reagent is added. Agglutination means that Ig is in the serum
2 findings on a peripheral smear for autoimmune hemolytic anemia
Marked microspherocytosis, Polychromatophils/reticulocytes
3 treatments for autoimmune hemolytic anemia
Immunosuppression - Prednisone 1-2 mg/kg/day, possible splenectomy
Treatment of comorbidities (ie. cold avoidance)
Transfusions depending on severity
Cause of hemolytic disease of the newborn or erythroblastis fetalis
Maternal IgG antigens attach to the surface of fetal RBCs caused by Placental abruption, maternal transfusion, pre existing maternal antibodies
Demographics for hemolytic disease of the new born
Rh- mother with Rh+ fetus, Most commonly ABO antibody issue, Most severe with Rh antibodies
Presentation of infant and mother in cases of hemolytic disease of the newborn
Newborn: Jaundice, Anemia, Positive direct coombs test, hepatosplenomegaly, Edema, Heart failure
Mother: Positive indirect coombs test
Before, After, and Preventative Care for Hemolytic disease of the newborn
Before:
Intrauterine fetal transfusion
Early induction of labor
Maternal Plasma exchange
After:
Transfusion
Supportive care
Prevantative
RhoGAM prevents Rh+/- immune response
What does RhoGAM do
Prevents Rh antibody formation, give it just after birth of Rh+ baby to Rh- mother
Cause of paroxysmal nocturnal hemoglobinuria
Acquired genetic defect leads to lysis of RBCs, deficit in complement regulating cell membrane proteins CD55 and CD59
Demographics of paroxysmal nocturnal hemoglobinuria
Most common in young adults
Can occur in patients of any age, equal in both genders and no evidence of heritability
Pathology of Paroxysmal Nocturnal Hemoglobinuria
RBCs are vulnerable to lysis by complement, MAC formation causes RBC destruction, free hemoglobin depletes nitric oxide
Presentation of Paroxysmal nocturnal hemoglobinuria
Episodic, heavier in the AM because of nightly drop in blood pH, venous constriction including ED and esophageal spasms, s/s of thrombosis
Life expectancy for significant Paroxysmal Nocturnal Hemoglobinuria
10-15 years
2 diagnostic tests for Paroxysmal nocturnal hemoglobinuria
Urine hemosiderin and Flow cytometry
Labs for paroxysmal nocturnal hemoglobinuria
everything decreased except for possibly reticulocytes and MCV
Treatments for Paroxysmal Nocturnal Hemoglobinuria
Mild - Observation only
Severe or aplastic anemia - Stem cell transplant
Severe hemolysis - Eculizumab
Supportive care for paroxysmal nocturnal hemoglobinuria (3)
Transfusion, Iron replacement, COrticosteroids
Acute Blood Loss Anemia
From external or internal hemorrhages trauma, GI bleed, etc
Chronic blood loss anemia
Anemia due to depletion of iron stores
3 Stages of blood loss anemia
Hypovolemia (CBC appears normal), Anemia (Hypovolemia is corrected and CBC is abnormal), Recovery (transient reticulocytosis)
Treatment for blood loss anemia
Consider investigative studies to find bleed
Transfusion
Fluid replacement
Supplemental iron
Most common cause of aplastic anemia
Idiopathic autoimmune suppresion of hematopoiesis
Diseases the can cause Aplastic Anemia (3)
Lupus, Paroxysmal nocturnal hemoglobinuria, transfusion related graft versus host disease
4 toxins that can cause aplastic anemia
benzene, toluene, insecticides, mercury
Medications that cause aplastic anemia (3)
Chemo, anticonvulsants, Sulfa drugs
Infections that cause Aplastic anemia (4)
hepatitis, Epstein barr, cytomegalovirus, Parvovirus B19
2 Other factors that can cause Aplastic anemia
radiation exposure, pregnancy
Presentation of aplastic anemia
Infections from decreased WBCs
Anemia from decreased RBCs
Bruising, bleeding, purpura/petechiae from decreased platelets
No hepato or splenomegaly
Labs of aplastic anemia
WBC
Platelets
Reticulocytes
MCV
MCH
WBC - decreased
Platelets - decreased
Reticulocytes - decreased or absent
MCV - normal or increased
MCH - normal
First line aplastic anemia treatment
Remove underlying factors
3 pharmacotherapies for aplastic anemia
Multilineage - Eltrombopag - Boosts all three
Erythropoietic - Epoetin, darbepoetin
Myeloid - Filgrastin, sargramostim
2 treatments for severe aplastic anemia
Bone marrow transplant or immunosuppression
3 options for immunosuppression in severe aplastic anemia
Equine ATG and cyclosporine
Steroids with ATG
Eltrombopag
Criteria for severe aplastic anemia (PLT, NEU, RTC)
Neutrophils below 500/mcL, Platelets below 20,000/mcL reticulocytes below 60,000/mcL
Difference between darbopoietin and epoetin
half life of darbepoetin is 3x longer
Black box warnings of EPO or DARBY (4)
Stroke or thrombosis, Cardiovasular issues in CKD, Tumor progressing, DVT
3 things to monitor for EPO or DARBY use
Iron status, Hb, BP
Sideroblastic anemia description
Mixed group of disorders that share abnormalities in heme synthesis and mitochondrial function - ring sideroblasts seen in bone marrow aspirate
MOA of sideroblastic anemia
Decreased Hb synthesis because of impaired ability to incorporate iron into protoporphyrin IX
Most common and two other causes of sideroblastic anemia
Most common - X linked
Can also be Autosomal recessive or mitochondrial
Ways sideroblastic anemia can be acquired (more common than inherited) (6)
General myelodysplastic syndrome
Chronic alcoholism
Lead poisoning
Copper deficiency
Chronic inflammation
Medications (isoniazid, linezolid, chloramphenicol)
5 common signs of ANY anemia
Fatigue, Tachycardia, Dizziness, Dyspnea on Exertion, Palpitations
Unique symptoms of sideroblastic anemia
Pallor of conjunctiva and palmar creases. May see s/s associated with myelodysplastic syndrome
Sideroblastic anemia labs
H/H
MCV
RDW
Reticulocytes
Total iron binding capacity
Transferrin saturation
Increased Ferritin
H/H - Decreased 20-30%
MCV - Often decreased but can be elevated in acquired
RDW - Usually increased
Reticulocytes - Normal or decreased
Total iron binding capacity - Normal or decreased
Transferrin saturation - Increased
Iron - Increased
Increased Ferritin - Increased
4 findings of a sideroblastic anemia peripheral smear
Basophilic stippling, Poikilocytosis, Anisocytosis, Polychromasia
What test must be done to make a sideroblastic anemia diagnosis and what should you see?
Erythroid hyperplasia
Ringed sideroblasts with a Prussian blue stain (erythroid cells with iron deposits in the mitochondria
Treatment for Sideroblastic anemia (5)
Correct underlying cause
Transfusions with severe anemia
Congenital may need B6 or B1 vitamins
Stopping medications
Genetic couseling
Most common cause of anemia world wide
Iron deficiency anemia
Percent of dietary iron that is usually absorbed
10%
Amount of iron normally lost from the body per day
About 1 mg per day
Effect of antacids on iron absorption
Decrease iron absorption
Role of hepcidin in iron absorption
Breaks down ferroportin to prevent iron release to the blood stream from GI tract cells
5 causes of iron deficiency due to iron loss
Deficient diet
Increased requirements (pregnancy, growth spurt)
Chronic blood loss (menstruation GI ulcers)
Decreased absorption
Iron sequestration
4 Signs of iron deficiency anemia
Classic anemic symptoms
Smooth tongue and Brittle nails, Koilonycha, Cheilosis in severe cases
Pica
Neuro - restless leg syndrome and developmental delay
Cheilosis
Inflammatory condition seem with anemia that causes scaling at the corners of the mouth
Plummer-Vinson syndrome
Seen in severe iron deficiency anemia - esophageal webs leading to dysphagia
Iron deficiency anemia Labs
H/H
MCV
MCH
Reticulocytes
Total iron binding capacity
Transferrin saturation
Iron
Ferritin
H/H - decreased
MCV - Normal early, dereased later
MCH - decreased
Reticulocytes - normal or decreased
Total iron binding capacity - increased
Transferrin saturation - decreased
Iron - decreased
Ferritin - decreased
3 stages of iron deficiency
Low iron without anemia, normocytic anemia, microcytic anemia
5 Peripheral smear findings for iron deficiency anemia
Hypochromic microcytic cells
Target cells
Poikilocytosis
Anisocytosis
Increased platelets
Oral supplementation for iron deficiency anemia
Ferrous sulfate 325 mg orally 3x per day on an empty stomach
How long should iron supplement therapy be continued after anemia resolution
6 months of longer
Effect on iron supplementation of taking with food or ascorbic acid
Food decreases absorption
Ascorbic acid increases absorption
How fast will hematocrit and reticulocytes rise with iron supplementation?
Hct halfway to normal in 3 weeks baseline in 2 months
Reticulocytes rise in 4-7 days peak in 1-1.5 weeks
3 contraindications to iron supplementation
Allergy, hemochromatosis, hemolytic anemia
Side effects of iron supplementation (5)
Constipation, N/V, dark stools, GI cramps, gray teeth or urine
Cutaneous siderosis
Skin staining from IM iron injections
4 Newer better parenteral iron treatments
Ferric carboxymaltose, ferumoxytol, iron sucrose, sodium ferric gluconate
MOA of anemia of infection
Proinflammatory cytokines lead to increased hepcidin which leads to decreased iron absorption and availability
Presentation of anemia of chronic inflammation
75% normocytic 25% microcytic
Decreased Iron
Increased or normal ferritin
Inflammatory process also present
Cause of anemia of CKD
Failure to secrete adequate EPO by the kidneys
Presentation of anemia of CKD
Known history of CKD with anemic symptoms
Normocytic, normochromic with normal iron studies
3 anemias of hypometabolic states
Endocrine anemia - normocytic normochromic anemia caused by decreased EPO secretion d/t endocrine undersecretion
Anemia of chronic liver disease - Cholesterol deposits on RBCs make them look bigger and last less time. More succeptible to hemorrhage
Anemia of starvation - Decreased protein to decreased metabolism to decreased EPO
Anemia of the Elderly - 3 causes and one diagnostic tip
Anemia caused by resistance to EPO, decrease in EPO secretion, and chronic low level inflammation. Anemic elderly patients with a negative work up for other etiologies
When is EPO useful in treating anemia?
In situations where EPO secretion is diminished
Daily utilization and absorption of B12
5mcg per day absorbed, 3-5 mcg per day used
Absorption and storage of B12
Absorbed in the ilieum and stored in the liver (2-5 mg)
5 causes of B12 deficiency
Dietary deficiency
Decreased intrinsic factor from pernicious anemia or gastric surgery
Pancreatic insufficiency
Transcobalamin II deficiency
Medications (PPI, Metformin, Colchicine)
Blind loop syndrome
Overgrowth of bacteria in the bowel compete for B12 use with the body
Presentation of B12 deficiency
GI - Nausea, anorexia, glossitis, angular cheilitis
Neuropathy
Neuropathy progression of B12 deficiency
Peripheral parasthesias, then difficulty with balance and proprioception, then cerebral function issues
Labs of B12 deficiency
H/H
MCV
MCH
MCHC
Serum B12
Homocysteine
Methylmalonic acid
Reticulocytes
WBC and platelets
LDH and Bilirubin
H/H - Decreased
MCV - Elevated
MCH - Elevates
MCHC - Normal
Serum B12 - Decreased (<200 deficiency, 200-300 equivocal)
Homocysteine - increased
Methylmalonic acid - increased
Reticulocytes - normal or decreased
WBC and platelets - normal or decreased
LDH and Bilirubin - increased due to intramedullary destruction by abnormal RBCs
4 findings for B12 deficiency on a peripheral smear
Hypersegmented neutrophils
Macro-ovalocytes
Bizarre RBC shapes
Basophillic stippling
2 labs used to detect pernicious anemia
Antiparietal cell antibodies
Gastrin levels
Neither test is highly specific, gastric biopsy also an option
Recommended B12 and folic acid therapy for B12 deficiency
1 mg of each per day, any route
Expected response to B12 deficiency treatment
Reticulocytosis in one week, Normal CBC in two months
4 side effects of PO B12
Headache, Parasthesias, GI upset, Glossitis
Maintenance monitoring for chronic B12 supplementation
CBC and B12 level every 3-6 months
Routine monitoring for B12 supplemetation (5)
B12 level, H/H, RBCs, Reticulocytes, iron and folate
Daily absorption, utilization and storage of folate
Absorbed 125 mcg/day Used 50-100 mcg per day we can store 5-10 mg
5 causes of folate deficiency
Dietary deficiency, Increased need (pregnancy, hemolytic anemia), Inhibition of reduction to active form (methotrexate), Excess loss (hemodialysis), Decreased absorption
Mnemonic to remember metabolic absorption sites
Dude is Just feeling Ill bro
Duodenum Iron, Jejunum Folate, Illeum B12
Presentation of folate deficiency
4 pertinent positives and 1 pertinent negative
Anorexia, nausea, glossitis, angular chelitis
NO NEUROPATHY
Folate deficiency labs
H/H
MCV
MCH
MCHC
Serum B12
Homocysteine
Methylmalonic acid
Reticulocytes
WBC and platelets
RBC folate and serum folic acid
H/H - decreased
MCV - elevated
MCH - elevated
MCHC - normal
Serum B12 - normal
Homocysteine - increased
Methylmalonic acid - normal
Reticulocytes - normal or decreased
WBC and platelets - normal or decreased
RBC folate and serum folic acid - decreased
Difference between RBC folate and serum folic acid
RBC folate is long term
Serum folic acid is recent intake
2 findings of Peripheral Smear for folate deficiency
Hypersegmented neutrophils, Macro ovalocytes
Recommended Folate Treatments
1-5 mg daily PO for 4 months
Levomethylfolate if the patient cannot metabolize folate to its active form
Response to folate deficiency Tx
Begin to see reticulocytosis in 1 week
CBC should normalize in 2 months
Side effects and monitoring for folic acid treatment
Malaise and nausea, monitor Hb
Polycythemia Vera
Excessive production of hematopoietic cells, especially RBCs
Essential thrombocytosis
Excessive platelet production
Myelofibrosis
Excessive production of collagen or fibrous tissue in the marrow
Chronic myelogenous leukemia
Excessive production of granulocytes
Presentation of myeloproliferative disorders (4)
Fatigue, Weight loss, Splenomegaly, Easy bruising
Why do myeloproliferative disorders cause anemias
Abnormal cell growth competes with and suppresses erythroid precursors
Lab work up to detect myeloproliferative disorders
CBC for anemia and WBC and PLT count
Bone marrow biopsy
Treatment for myeloproliferative disorders
Myelosuppression or bone marrow transplant for CML or myelofibrosis. Observe if asymptomatic
4 phases of hemostasis
Platelet plug
Clotting cascade
Termination of cascade
Fibrinolytic clot removal
Lifespan of a platelet
10 days
Fraction of platelets sequestered in the spleen
One Third
Normal Platelet Count
150,000-450,000
Contents of Platelet Dense Granules (4)
Serotonin, ADP, ATP, Calcium
6 Alpha granule contents
Platelet derived growth factor, Transforming growth factor, Fibrinogen, VW factor, Platelet factor 4, Factor V
What do platelets release to activate other platelets
Thromboxane
3 functions of Von Willebrand factor
Binds to endothelium and promotes platelet adhesion
Plasma carrier for factor VIII
Binds to exposed collagen
Source of activation for intrinsic and extrinsic clotting cascades
Intrinsic - Found in Blood
Extrinsic - Tissue factor
Common joining point of extrinsic and intrinsic clotting cascades
Factor X
Factors involved in the extrinsic, Intrinsic, and common Pathways
Extrinsic - 3 and 7
Intrinsic - 12, 11, 9, 8
Common - 10, 2, 1
4 Things cleaved by Thrombin (Factor II)
Factors 5 and 8, Fibrinogen, Thrombomodulin
Vitamin K dependent factors
2,7,9,10, Proteins C and S
2 Factors not made in the liver only
3 and 5
Three things that join to cleave factor 10
9a, 8a, and Calcium
Action of proteins C and S
Inhibit the conversion of prothrombin to thrombin by inhibiting factors V and VII
Antithrombin (III)
Inactivates factors of the intrinsic pathway, especially 10
Accelerated 1000x with heparin
Fibrinolysis Cascade
Plasminogen is activated to Plasmin by t-PA which breaks down fibrin
What does a D dimer test look for
Fibrin degradation products
Universal donor for Blood
O negative - give in an emergency
Transfusion recommendations for hemodynamically stable patients without active bleeding
Hgb<6 - recommended
Hgb 6-7 - likely indicated
Hgb 7-8 Consider depending on clinical status
Hgb 8-10 Generally not indicated but should be considered for active bleeding, ischemia, etc.
Hgb >10 Not indicated
How much does one unit of PRBCs increase patient hemoglobin
about 1g/dL
How long do you need to wait after a transfusion to assess patient hemoglobin
15 minutes
4 most frequent transfusion reactions
Fever, chills, pruritis, urticaria (hives)
MCC of death in transfusion patients and treatment
Circulatory overload - use diuretics
Transfusion reaction common in smokers and alcoholics
Transfusion related acute lung injury
Whole blood
Only used in cases of massive hemorrhage - hard to preserve
Volume of 1 unit PRBCs
200mL
3 flavors of Packed Red Blood Cells
Leukocyte reduced (performed on most blood products
Irradiated - Avoid graft versus host disease
Washed - gets rid of protein remnants that may cause a reaction
Universal plasma donor and universal plasma recipient
UD - AB+
UR - O-
Fresh Frozen Plasma
Used to replace deficient clotting factors, must be used within 24 hours of being thawed or factors 5 and 8 begin to decline
Cryoprecipitate
Collected by thawing plasma at 4 degrees Celsius and collecting the white precipitate which is rich in VWF, 8, 13, and Fibrinogen
Allows for the same amount of replacement at a lower volume
Indication for clotting factor concentrates
Specific factor deficiencies such as hemophilia A or B
4 indications for platelet transfusion based on platelet counts (4)
- Platelet count under 10,000 to prevent spontaneous hemorrhage
- Platelet count under 50,000 who are actively bleeding, scheduled for an invasive procedure, or have an intrinsic platelet disorder
- Count under 100,000 who have a CNS injury, multisystem trauma, or scheduled neurosurgery
- Patients with normal levels and ongoing active bleeding or a reason for platelet dysfunction such as aspirin therapy or uremia
How much should a unit of platelets increase the platelet count?
5,000-10,000
4 Hemostasis promoting agents
Protamine sulfate
Vitamin K
Desmopressin
Thrombin
Protamine sulfate
MOA, Use, Concerns
Neutralizes heparin and is used for that purpose during surgery or dialysis procedures. May result in severe hypotensive or anaphylactoid like reactions
Vitamin K (Phytonadione)
MOA, Uses, Concerns
Reverses Warfarinused to treat vitamin K deficiency hepatic metabolism and renal and fecal excretion
Desmopressin MOA, use, and route
3 factors it targets
Test it effects
1 Adverse effect
2 Routes
Increases plasma VW factor, factor 8, and t-PA contributing to a lower aPTT and bleeding time, used for hemostasis and may lead to hyponatremia. IV or Intranasal
Topical thrombin MOA, use, and contraindications
Converts fibrin to fibrinogen and is applied directly at site of bleeding. Used in surgery for minor bleeding. Contraindicated in large vessels or sensitivity to bovine products
3 types of antithrombotic drugs
Antiplatelet drugs, Anticoagulants, Fibrinolytic agents
General MOA, Indication, and Contraindication for anticoagulants
MOA varies for each drug
Most commonly for venous thrombosis although can be for any clotting situation
Contraindicated in bleeding, renal problems, allergies
4 Parenteral anticoagulants
Unfractionated heparin, Low-molecular weight heparin, Bivalirudin, Argatroban
MOA of unfractionated heparin and cautions
Binds to antithrombin III, no adjustments needed in renal patients, pregnancy category C
Monitoring for Unfractionated heparin
Use the PTT or factor Xa level for monitoring
4 adverse effects of unfractionated heparin
Bleeding, Thrombocytopenia, Osteoporosis, Elevated LFTs
7 Contraindications of unfractionated heparin
HIT, hypersensitivity, Active bleeding, hemophilia, PLT less than 50k, purpura, severe hypertension
Heparin Induced THrombocytopenia
HIT - affects 3% of those exposed to heparin. Heparin and PF4 form a neoantigen on the PLT surface which induces immune response, splenic platelet clearance and platelet activation. Patients who have had HIT can never have heparin again
HIT risk factors and monitoring
Patients new to heparin or on long term heparin, watch CBC for a drop in PLT count over 50% as well as necrosis, bruising or lesions at the injection sites
4 Ts of HIT scoring and score interpretation
Thrombocytopenia, Timing of platelet count fall, Thrombosis or other sequelae, Other causes of thrombocytopenia
4-5 is intermediate
3 confirmatory tests for HIT
HIPA, Serotonin release assay, Heparin-PF4 Ab ELISA
4 substitutes for heparin in the case of HIT
Argatroban, danaparoid, fondaparinux, bivalirudin
What should we use for long term anticoagulation after HIT and how long should it be used?
Warfarin 2-3 months if no thrombosis occured
3-6 months if thrombosis did occur
How should HIT be listed in a patients chart
As a “heparin allergy”
MOA route and half life of Low molecular weight heparin
Enhance inhibition of Antithrombin III, SC injection allowing for outpatient and 4 hour half life but not compatible with dialysis
3 Indications and 1 contraindication of Low molecular weight heparin
Prophylaxis of venous thromboembolism, DVT or PE, Acute coronary syndrome
Mechanistic difference between heparin types
Unfractionated heparin causes AT III to bind both Xa and THrombin Low molecular weight heparin only binds Xa
When is monitoring for LMW Heparin recommended (3 things) and what should one monitor (1 thing)?
Pregnancy, CrCl 30 or under, Morbid obesity
Monitor anti Xa levels
Adverse effects, Pregnancy category, and contraindications for LMW heparin
Bleeding, HIT, and osteoporosis (but less common than with unfractionated)
Pregnancy category C
Contraindicated in active bleeding or HIT hx
5 advantages of LMW Heparin over Unfractionated heparin
Better bioavailability and longer half life, Dose independent clearance, More predictable anticoagulation response, Lower HIT risk, Lower osteoporosis list
When should we “bridge” a patient from Warfarin to Lovenox before or after elective surgery or invasive procedures (4)
Embolic stroke within the past 3 months
Previous embolic stroke during interruption of anticoagulation
Mechanical heart valve
Atrial fibrillation in pt with high stroke risk
MOA of argatroban (Acova)
Directly and selectively binds to the thrombin active site of free and clot associated thrombin
Inhibits fibrin formation, activation of coagulation factors V, VIII, and XIII, activation of protein C and platelet aggregation
Metabolism of argatroban
Hepatic - caution with liver impairment
2 indications, 1 adverse effect, and pregnancy category of Argatroban
Ind: HIT and Percutaneous coronary intervention
SE: bleeding
Pregnancy category B
MOA and half life of bivalirudin
Direct highly sensitive thrombin inhibitor, reversibly binds to thrombin active site and has a 25 min half life
Indications and clearance for Bivalirudin
Renal clearance
Alternative to heparin in percutaneous coronary intervention especially in those with hx of HIT - Used a lot in Cath labs
MOA and monitoring for Warfarin
Inhibits vit K and therefore factors II, VII, IX, X. Hepatic metabolism with 36 hour half life and takes 5-7 days for full effect. Monitor PT and INR
Pregnancy category for warfarin
Pregnancy D for heart valve, X for all others - don’t use
Does not pass into breast milk
Indications (3) and Adverse reactions (2) for Warfarin
DVT or PE prophylaxis, embolic complications from A fib and cardiac valve replacement - adjust dose according to INR starting w/ 5mg per day
Adverse effects: Bleeding - variable. Necrosis due to paradoxical thrombosis in limbs, breast or penis occurs when started w/o LMW Heparin
Effect of ethanol on warfarin
Acute binges increase PT/INR
Chronic use decreases PT/INR
3 random facts about HIT
More common in females
More often involves Venous thrombosis
More common in surgical patients
4 direct oral anticoagulants and what they inhibit
Dibigatran (Pradaxa) - Thrombin
Rivaroxaban (Xarelto) - Xa
Apixaban (Eliquis) - Xa
Edoxaban (Savaysa) - Xa
Indications for dabigatran (3)
Stroke prevention in nonvalvular atrial fibrilation, DVT/PE, DVT/PE prophylaxis after hip or knee arthroplasty
Contraindications, Adverse events, Antidote, and metabolism of dabigatran
ESRD or HD contrindicated, Can lead to bleeding especially GI bleeds, Reversed by Praxbind (idarucizumab), renal metabolism
3 drug interactions for dabigatran (KTC)
Ketoconazole, Cyclosporine, Tacrolimus
3 Indications for Ravaroxaban (Same as dabigatran)
Stroke prevention in nonvalvular atrial fibrilation, DVT/PE, DVT/PE prophylaxis after hip or knee arthroplasty
Metabolism of Rivaroxaban and 2 contraindications
Hepatic CYP 3A4 avoid combination with CYP inhibitors
Contraindicated in ESRD, reduce dose if CrCl less than 50
Contraindicated in active pathologic bleeding
Antidote for Rivaroxaban
AndexXa (andexanet alpha)
MOA of apixaban (Eliquis)
Inhibits platelet activation and clot formation via direct selective and reversible inhibition of free and bound active factor X
Indications of apixaban (Same as dagatroban and rivaroxaban)
Stroke prevention in nonvalvular atrial fibrilation, DVT/PE, DVT/PE prophylaxis after hip or knee arthroplasty
Metabolism and Half life of apixaban (Eliquis)
Renal and hepatic including CYP3A4, 12 hour half life
Adverse event, antidote and Contrindication of apixaban (Eliquis) same as rivaroxaban
Bleeding is the most severe adverse event, contraindicated in active pathologic bleeding. AndexXa (andexanet alfa) is the antidote
MOA and indications of Edoxaban with renal dosing
Factor 10 inhibitor that does not require antithrombin 3 for activity. Used for stroke prevention in nonvalvular atrial fibrilation, DVT/PE Cannot use if CrCl over 95
Metabolism of edoxaban (Savaysa) and time to peak plasma conc.
Hepatic primarily with CYP 3A4, peak reached in 1-2 hours with a 10-14 hr half life
NO ANTIDOTE
Direct oral anticoagulant with the highest bioavailability
Rivaroxaban (80%)
Lab tests needed with DOACs
No lab tests needed - less burden on patients than Warfarin
MOA of aspirin
Irreversibly binds to COX enzymes and prevents the production of thromboxane A2, take 20-45 minutes to take effect
Dose range for aspirin
75-325mg daily
Indication for aspirin (3)
Primary prophylaxis of MI, Secondary prevention in patients with a history of vascular events, other vascular diseases
When should aspirin be given in relation to NSAIDS and why?
60 minutes prior or 8 hours after
Because NSAIDs and ASA will compete at the COX-1 catalytic site
3 adverse events related to aspirin
GI bleeding, Dyspepsia, ASA allergy
MOA of clopidogrel (Plavix)
Time to take effect
Irreversibly inhibits ADP pathway of platelets but requires metabolic activation and takes 3-5 days for full effect
2 indications for clopidogrel (Plavix)
Primary MI prophylaxis, standard prevention in patients with history of vascular events
Adverse events, dosage adjustment, drug interaction and note about clopidogrel(plavix)
Bleeding is most serious complication
No hepatic or renal adjustment is necessary
Interacts with Omeprazole or Esomeprazole (effectiveness is decreased)
Genetic mutation may confer Plavix resistance
MOA of Prasugrel (effient)
The active metabolite actively blocks P2Y12 component of ADP receptors on the platelet
Duration of action of Prasugrel (effient)
5-9 days; takes effect in 2-4 hours
Dose adjustment and contraindications for Prasugrel (Effient)
No does adjustment needed for hepatic or renal
Contraindicated in patients with a hx of TIA(Transient Ischemic Attack) or CVA (Cerebrovascular Accident)
MOA of ticlodipine (Ticlid)
Irreversibly blocks P2Y12 component of ADP recenptors which prevents activation of GPIIb/IIIa receptor complex, thereby reducing platelet aggregation
Hepatic/Renal Dose adjustments for ticlodipine (Ticlid)
No hepatic or renal dose adjustment
4 dangerous potentials adverse effects associated with Ticlodipine (Ticlid)
Neutropenia
Agranulocytosis
Thrombotic thrombocytopenic purpura
Aplastic anemia
Monitoring of Ticlodipine (Ticlid) and timing of TTP, neutropenia, and aplastic anemia
CBC w/ diff every 2 weeks
TPP most common 3-4 weeks
Neutropenia most common at 4-6 weeks
Aplastic anemia most common after 4-8 weeks
MOA of ticagrelor (Brilinta)
REVERSIBLY and noncompetitively binds the Adenosine phosphate receptor on the platelet surface which prevents ADP mediated activation of the GPIIb/IIIa receptor complex thereby reducing platelet aggregation
NO metabolic activation
Duration of Ticagrelor (Brilinta) effect and route
About 3 days, PO
Contraindication and Black box warning for ticagrelor (Brilinta)
Contraindicated with severe liver disease (but no hepatic or renal dosing. Also contraindicated in active bleeding
Reduced effectiveness when taken with ASA over 100mg per day
MOA of Kengrelor (Kengreal)
REVERSIBLY and noncompetitively binds the Adenosine phosphate receptor on the platelet surface which prevents ADP mediated activation of the GPIIb/IIIa receptor complex thereby reducing platelet aggregation
IMMEDIATE ONSET!!
Indication for Cangrelor and route
IV only, for patients undergoing percutaneous coronary intervention
Contrindicated for bleeding patients
Transition from IV Cangrelor to Oral ticagrelor, clopidogrel or prasugrel
for ticagrelor give loading dose immediately after or during infusion
For Clopidogrel and Prasugrel only AFTER the IV infusion is complete
3 irreversible P2Y12 inhibitors
Ticlodipine, Clopidogrel, Prasugrel
2 Reversible P2Y12 inhibitors
Ticagrelor, Cangrelor
MOA of Epitifibatide (Integrilin) and Abciximab (Reopro)
Gp IIB/IIIA inhibitors, block receptors and inhibit platelet aggregation and activation
Route of Epitifibatide (Integrilin) and Abciximab (Reopro) as well as peak time and length of duration
IV only, can be given with a bolus dose
Peak reached at 30 minutes after administration lasts from 24-48 hours
Tow indications for Epitifibatide (Integrilin) and Abciximab (Reopro)
Patients undergoing PCI, high risk with stable angina
Side effects of Epitifibatide (Integrilin) and Abciximab (Reopro)
Bleeding and thrombocytopenia
Usage and MOA of fibrinolytics
Rapid dissolution of thrombi in life threatening situations - converts plasminogen to plasmin which breaks fibrin into fibrin degradation products
Administrative route of fibrinolytics
Systemic for acute MI, stroke and massive PE
Peripheral for DVTs and arterial thrombosis can be delivered directly into the thrombus
MOA of Alteplase (tPA)
Preferentially activates plasminogen that is bound to fibrin - in theory this results in clot dissolution
4 indications of Alteplase (tPA)
PE with hemodynamic instability, acute STEMI, Severe DVT, asending thombophlebitis
How soon does tPA or Alteplase need to be givien for a stroke?
Within 3 hours of onset
MOA of streptokinase
A streptococcal protein; Catalyzes the conversion of inactive plasminogen to active plasmin
Administration and indications (4) of streptokinase
IV for PE with hemodynamic instability, Acute STEMI, severe DVT and ascending thrombophlebitis
Contraindicated in those with antistreptococcal antibodies
NOT recommended for Ischemic stroke
A few meds that can cause thrombocytopenia (4)
NSAIDs, Fish oil, anticoagulants/antiplatelets, some herals
How might you distinguish a bleeding/bruising disorder from abuse?
Abuse will show bruises in various stages of healing
4 initial tests to run for a diagnostic evaluation on a bleeding patient
CBC, Peripheral blood smear, Coagulation Panel (PT, PTT, INR), CMP (includes LIVER function)
2 additional tests that you MIGHT want to run for a bleeding patient
Bleeding Time, Platelet aggregation study
Bleeding Time Test
1-2 Standard incisions made on arm
BP Cuff put on and inflated to 140 mmHg
Measure by blotting blood with filter paper every 30 seconds
Normal 3-8.5 seconds
Why might we want a CMP rather than a BMP on a patient with a bleeding disorder?
It will tell us about the patient’s LIVER function
Platelet function analyzer
Puts whole blood through a capillary lined with platelet agonists and measures the time to the occulsion of the membrane
Coagulation Panel elements (3)
PT/PTT/INR
PTT (Partial thromboplastin time)
Measures intrinsic pathway by adding factor XIIa used to monitor HEPARIN
Normal PTT value
21-35 seconds
PT (Prothrombin time)
Measures extrinsic pathway by adding factor VIIa used to monitor WARFARIN
Normal PT value
11-13 seconds
INR
International Normalized Ratio
Ratio of a patients prothrombin time (PT) to a control sample raised to the ISI value of the tissue factor used for the test
INR interpretation
Normally .8-1.2
2-3 on Warfarin
Higher INR=Higher bleed risk
Hemophilia A
Congenital deficiency resulting in deficiency of coagulation factor VIII - X linked recessive
Hemophilia B
Congenital deficiency of coagulation factor IX - X linked recessive
Initial presentation of hemophilia
Presents in infancy or early childhood with joint and soft tissue bleeding
In patients with more mild hemophilia, patients present with more bellding than usual in SOME circumstances (ie. surgery)
Common complication in hemophilia
Patients develop inhibitors to the clotting factors that they are missing
Lab findings of hemophilia
Normal CBC
Normal PT/INR
Prolonged aPTT
Severity determination for hemophilia
Use factor assays showing activity levels (50-150 % is normal for factor VIII)
Mild 5-40% of normal
Moderate 1-5% of normal
Severe Less than 1% of normal
Treatment of hemophilia
A - DDAVP (Desmopressin) for mild, Factor VIII concentrate for bleeding episodes or severe condition
B - Factor IX concentrate for all severity levels
Treat for 3-10 days after surgery
Treatment for hemophilia related arthritis
Celecoxib - a COX2 selective NSAID (do not use aspirin)
Prognosis for hemophilia
Moat will live full, normal lives with proper treatment - causes of death include hepatitis, transfusion related HIV/AIDS and intercranial bleeding
Patient education for hemophilia
Avoid contact sports, home infuse if needed and watch for signs of bleeding
Role of Von Willebrand factor
Tethers platelets to the site of vascular injury
Type 1 VWD
Autosomal dominant with no to severe bleeding. Quantatative defect
Type 2 VWD
Usually autosomal dominant but can be recessive. Qualitative defect with moderate to severe bleeding
Type 3 VWD
Autosomal recessive profound quantitative defect that presents with severe bleeding
Clinical Features of vWD
Nosebleeds and hematomas
Prolonged bleeding from trivial wounds
GI bleeding is NOT common
Women are five times as likely to have menorrhagia
Laboratory findings for vWD
Prolonged bleeding time (not specific) may be normal
Mildly prolonged aPTT (depends of severity)
NORMAL PT
Can measure vWF but may need multiple tests to confirm diagnosis
2 treatments for vWF
DDAVP (Desmopressin) for milder bleeding
vWF or Factor VIII concentrates in more severe situations
Refer to hematology
Factor XI deficiency
Sometimes referred to as hemophilia C
Autosomal recessive and common among Ashkenazi jews
Treat with Factor XI or FFP if factor is not available
Thrombocytopenia
Too few platelets results in mucous membrane, gum, and GI bleeds or even cerebral hemorrhage - can result from increased destruction and decreased production
Normal Platelet count and risks at:
Less than 100,000
Less than 50,000
Less than 10,000
150k-400k per microliter
At less that 100k - increased bleeding/complication during invasive procedures in enclosed spaces
At less than 50k - increased bleeding during invasive procedures and in trauma
At 10k - Risk of spontaneous hemmorhage
One way to be sure the spleen is enlarges
If you can see or feel it
5 potential causes of Destructive/Consumption thrombocytopenia
Splenomegaly
Antibody mediated destruction
Drug related destruction
Massive bleeding
Diffuse thrombi
Mechanism of Splenomegaly/Hyperspleen
Splenic clearance is upregulated - treatment may require a splenectomy
Immune thrombocytopenic purpura
Form auto-antibodies against antigens on the PLT surface which results in their destruction - Diagnosis of exclusion
Presentation of ITP
sudden purpuric rash, may also have bleeding (ie. gums) - 3% need blood transfusions
Diagnostic criteria for ITP
PLT count under 100k with all else normal
No other clinically apparent reason
Treatment for ITP (5)
Watchful waiting - intervene in the case of life-threatening circumstances. Avoid anticoagulants.
Corticosteroids are first line pharmacotherapy
IVIG, PLT transfusions and Splenectomy may be needed
Drug related PLT destruction MOA and Presentation
Usually immune mediated. Presents with mucocutaneous bleeding 7-14 days after exposure to a new drug
10 drugs that can lead to thrombocytopenia
(KNOW 3)
ANTIBIOTICS ESP. KNOWN FOR THIS
Abciximab, Vancomycin, Amiodarone, Cimetidine, Carbamazepine, Ibuprofen, Heparin, Rituximab, Tacrolimus, Immunizations
Treatment of Drug-Related PLT destruction
Stop problem medication, corticosteroids MAY be needed to reduce antibody titer
Bleeding associated platelet consumption
Bleeding patient looses platelets faster than they can make them
Hyperproliferative Thrombocytopenia - 4 potential causes
Leukemia/Aplasia, Metastasis to the bone marrow, Severe viral infections, Radiation of chemotherapy
Usual etiology of Qualitative platelet disorders
Usually Iatrogenic or acquired - not usually congenital
Good tool for picking up a qualitative platelet disorder
Peripheral blood smear
General presentation of qualitative PLT disorder
Bleeding of mucous membrane that can be corrected by transfusion of platelets
How soon should a reversible vs. Irreversible platelet drug be stopped before surgery
Irreversible needs to be stopped a week before (5-10 days)
Reversible needs to be stopped a couple of days before (1-2 days)
2 irreversible and 1 reversible platelet inhibitor
Irreversible - Aspirin and Clopidogrel
Reversible - NSAIDs
2 thrombotic microangiopathies
Thrombocytic thrombotic purpura
Hemolytic uremic syndrome
Thrombocytic thrombotic purpura mechanism
Rare disease
Idiopathically, large multimers of vWF are formed in the blood stream and the body does not have ADAMTS13 to break them down
Clinical presentation of thrombotic thrombocytopenic purpura
Acute or subactue symptoms related to neurologic dysfunction, anemia or thrombocytopenia
Fever
Dark urine
4 diagnostics for thrombotic thrombocytopenic purpura diagnostics
Normal or slight elevation in WBC cunt
Depressed hemoglobin 8-9 g/dL
20k to 50k platelet count
Moderate to sever schistocytosis
Four lab results for thrombotic thrombocytopenic purpura
D dimer - for clots
High LDH About 1k
High fibrinogen
Negative direct coombs test
Therapy for TTP
Plasma exchange or transfusion if exchange is not possible - DO NOT GIVE PLATELETS
6 possible second line treatments for TTP
Corticosteroids, rituximab, IVIG, vincristine, cyclophosphamide, splenectomy
Hemolytic Uremic Syndrome pathology
Clinical syndrome of progressive renal failure cause by microangiopathic hemolytic anemia and thrombocytopenia - most common cause of acute renal failure in children
Clinical features of HUS -5
Prodromal gastroenteritis
Lethargy
Seizures
Renal failure
Anuria
Common cause of HUS
Secondary to E. coli 0157:H7 Shiga like toxin production 70-85 % of patients recover renal function
Can also be familial
Labs for HUS (3)
Elevated BUN/CR
Thrombocytopenia with schistocytes
Check stool for E. coli and shigella
Treatment for typical and atypical HUS
Typical - supportive care NO plasma exchange
Atypical - Plasma exchange
Disseminated intravascular coagulopathy
Many clots form around the body
aPTT and PT are increased
Fibrinogen and PLT are decreased
The body is forming clots faster than it can break them down
Etiologies of DIC (Stop Making New Thrombi)
Sepsis
Trauma
Obstetric complications
Pancreatitis
Malignancy
Nephrotic syndrome
Transfusion
Clinical features of DIC
Bleeding at multiple sites including intravenous catheters or incisions. Purpura and petechiae
Lab findings for DIC
Progressive thrombocytopenia
Pronged aPTT and PT
Low fibrinogen
Elevated D-dimer
Schistocytes due to shearing of RBCs in accluded vessels
Goals for DIC patient levels of:
PLT
Fibrinogen
PT and aPTT
Hgb
PLT - over 20,000
Fibrinogen - over 80-100 mg/dL
PT and aPTT - under 1.5xNormal
Hgb - over 8 g/dL
6 steps in DIC treatments
Assess for underlying cause
Establish baseline for PT, aPTT, d-Dimer, fibrinogen
Transfuse blood products but only when needed
Follow PLT, aPTT/PT, fibrinogen every 4-6 hours
Consider using heparin if the patient is bleeding (counterintuitive)
Monitor until resolved
4 presentations of arterial thrombosis
MI, CVA, Limb ischemia, mesenteric ischemia
5 presentations of venous thrombosis
DVT and PE
Virchow’s triad of thrombosis
Stasis, Vessel wall injury, Hypercoagulability
Two factors that can lead to vessel wall abnormalities that can lead to thrombosis
Infection and inflammation
2 most common causes of a DVT
Stasis and hypercoagulability
Do thrombophillic disorders increase the risk of a venous thrombosis, and arterial thrombosis or both?
Venous thrombosis only
6 Vitamin K dependent factors
2,7,9,10, S, C
Prevalence of factor V Leiden
5% (1-15% of white people)
2 Mechanisms of Factor V Leiden
Factor V Leiden is inactivated more slowly by APC
There is a missing cleavage product of factor V that prevents it from stimulating protein C
How would the addition of protein C effect the PTT of a person with factor V leiden
It would stay the same
Treatment for Factor V leiden
Heparin for clots, only prophylax in cases of high risk surgery, pregnancy, and additional thrombophillic mutations
How can pregnancy cause a DVT
Uterine compression of the Left iliac atery
Prothrombin gene mutation
Causes a 30% higher plasma prothrombin load in heterozygous carriers
Protein Clot Stoppers
Protein C and S
Protein C deficiency inheritance pattern and prevalence
Autosomal dominant
1-9% of patients with venous thrombosis
1 in 200k to 300k newborns
Homozygous protein C deficiency causes…
Purpura fulminans neonatalis (widespread venous thrombosis and skin necrosis)
Risk factor for Warfarin induced skin necrosis
Protein C deficiency
Two factors regulated by protein C
Factors VIII and V
Inheritance pattern for protein S deficiency
Autosomal dominant
6 mechanisms of acquired protein S deficiency
Pregnancy, Oral contraceptive use, sickle cell anemia, inflammation, nephrotic syndrome, coumadin theraoy
4 factors inactivated by antithrombin III
IXa, Xa, XIa, XIIa
Inheritance of antithrombin III
Autosomal dominant
Prevalence and common clot sites for ATIII deficiency
Risk of thrombosis increases with age, most common sites are deep leg veins and mesenteric veins
When is pregnancy related thrombosis most likely to occur?
The six weeks following delivery (puerperium)
Antiphospholipid syndrome
Acquired hypercoagulable condition in which antiphospholipid antibody is found in the blood. Exact mechanism is not understood fully and results from a variety of effects of aPL upon coagulation
4 conditions caused by APS with prevalence rang
9-14% of patients with pregnancy losses, CVA, MI, DVT
2 conditions for which anti-phospholipid syndrome should be considered as a DDx
Young strokes, multiple pregnancy losses
2 hallmarks of APS
Pregnancy losses and thrombotic events
Percentage of untreated DVTs that progress to PE
50%
Two congenital defects that can cause a DVT to relocated to systemic arterial circulation
Patent foramen ovale
Atrial septal defect
4 symptoms of a DVT
Swelling, pain, discoloration, warmth in affected extremity
5 symptoms of a pulmonary embolism
SOB, Tachypnea, Pleuritic chest pain, cough/hemoptysis, hypotension
8 Wells criteria for DVT probability and interpretation
Active cancer
Paralysis
Bedridden 3 days within 4 weeks
Localized tenderness
Entire leg swollen
3 cm difference in calf size
Pitting edema
Collateral veins
0 - low probabilit
1-2 Moderate
3+ High
Approach of choice for DVT testing
Venous doppler ultrasonography
What is a D-dimer test best for
Ruling OUT rather than ruling IN a DVT
4 diagnostic tests for a PE workup
Angiography
Ventilation perfusion scan
CT scan with contrast
D-dimer
3 objectives in DVT treatment
Prevent further clot extension, prevent acute PE, reduce the risk of recurrence
Combination treatment for an acute DVT
Heparin AND Warfarin PO
Monotherapy for acute DVT/PE (4 options)
Pradaxa, Xarelto, Eliquis, Savaysa
DOACs
Target INR for DVT therapy w/ heparin and warfarin
2.5 (2-3 is acceptable)
When might you consider thrombolytics for a PE/DVT (3)
Unstable patient, Massive iliofemoral thrombosis, low bleed risk
When might you use and IVC filter (2 reasons) and what is one?
Inferior Vena Cava Filter
Contraindication for anticoagulant therapy/ high PE risk
Recurrent DVT despite anticoagulation therapy
4 initial tests and 2 follow up tests when you suspect a clotting disorder
Antithrombin, Protein C, Protein S, Factor V Leiden
Prothrombin gene, Antiphospholipid antibodies
How to confirm thromboembolic related tests
Repeat them in 2-3 months
Effect of Warfarin, Heparin and acute illness on thrombophilia workup
Warfarin - reduces protein C&S levels
Heparin reduces Antithrombin levels
Acute illness can effect levels of ANY anticoagulant
Duration of heparin therapy for DVT/PE
5 days or until ideal reange INR is reached
4 indicators for long term anticoagulation therapy
2 or more spontaneous events for all high-risk patients
1 spontaneous life-threatening thrombosis
1 spontaneous thrombosis at an unusual site (cerebral or mesenteric)
1 Spontaneous thrombosis in association with another clotting abnormality
