Clinical Medicine Exam 5 Heme/Onc Flashcards
Blood Percentages
Plasma
55% of whole blood
Water 92%
Other solutes
electrolytes, nutrients, respiratory gases, waste
Proteins 7% (by weight)
Albumin 58%
Globulins 37%
Fibrinogen 4%
Regulatory proteins <1%
Blood Percentages
Erythrocytes
RBC
44% of whole blood
Blood Percentages
Buffy coat
<1% of whole blood
Platelets 150-400,000
Leukocytes 4.5-11,000
Neutrophils 50-70% Basophils 0.5-1% Eosinophils 1-4% Lymphocytes 20-40% Monocytes 2-8%
Blood volume
Approx. 5 liters
2 liters cellular/solid
3 liters plasma/liquid
How long do blood cells survive?
Platelets = 7-10 days RBC's = 120 days WBC = vary by type
Formed elements of the blood
Erythrocytes
Buffy coat
Primary site of blood cell creation after birth
Bone marrow
Granulocytes
Neutrophil (bacteria)
Eosinophil (parasites)
Basophil (inflammatory)
Polynuclear, granules in cytoplasm
Agranulocytes
Natural killer cells
Lymphocytes ( 3types)
B cells
T helper cells
T suppressor cells
Monocytic cells (become macrophages)
Mononuclear, no granules
What is stem cell for blood cells
Hematopoietic stem cell
becomes two types of progenitor cells
Common myeloid progenitor cells
Common lymphoid progenitor cells
What do Common myeloid progenitor cells become
RBCs platelets macrophages neutrophils eosinophils basophils
What do Common lymphoid progenitor cells become
Plasma B cells Memory B cells T suppressor cells T helper cells Cytotoxic T cells
Interleukin 4 is specific for
Basophils
Interleukin 5 is specific for
Eosinophils
Where is erythropoietin made
Peritubular interstitial cells of the kidney
Then goes to red bone marrow and stimulates accelerated red blood cell production.
This increases O2 transport
Takes 3-7 days
Red blood cell production cycle
Erythropoietin Normoblast (uncommitted stem cell) Reticulocyte (nucleus ejected) RBC Diapedesis Capillary
EPO Drugs
Exogenous EPO creates more red blood cells increases O2 transport increases hematocrit thickening blood make the blood more difficult to pump creates stress on heart, arrest, etc.
RBC structure
Anucleated
O2 binds reversibly to heme
CO2 bonds reversibly to globin
CO binds almost irreversibly
Hemoglobin
4 O2 molecules per molecule
when O2 is bound it is oxyhemoglobin
When CO2 is bound it is carbaminohemoglobin
Hemoglobinopathies
Sickle Cell
Thalassemias
Mutations can occur resulting in abnormal hemoglobin that lead to hemoglobinopathies
RBC Break down
Liver and spleen
Red pulp of spleen (erythrocyte graveyard)
hemoglobin broke into heme and globin
Heme broken down into iron and bilirubin.
(Iron reused, bilirubin excreted)
Globin hydrolyzed into free amino acids
Nutrients needed for RBC produciton
B12
Iron
Amino acids
Folic acid
Free iron
Free iron is toxic
Eosinophils
Eosinophils are inflammatory cells that defend against parasitic infections.
Basophils
Basophils release histamine, causing the inflammation of allergic and antigen reactions.
Monocytes
Monocytes migrate from the blood stream and become macrophages.
Lymphocytes
Lymphocytes contain three cell types that participate in the immune system.
B cell
T Helper cell
T Suppressor cells
Cytokines in Blood cell Production
Cytokines differentiate what type of blood cell forms
RBC of abnormal / varying sizes
Anisocytosis
Large RBC
Macrocytes
Small RBC
Microcytes
Irregular shape RBC
Poikilocytosis
RBC’s With Burrs (crenated)
Echinocytes
RBC fragments
Schistocytes
RBC with less color
Hypochromic cells
Where do platelets come from
megakaryocytes
Steps in coagulation
Trauma - Vascular Spasm
Formation of temporary plug (platelet plug)
Blood coagulation (Clot - Fibrin mesh)
repair & fibrinolysis
Extrinsic clotting factors
- The extrinsic pathway starts with the exposure of blood clotting factors to the tissue factor, TF, in the extravascular tissue.
This pathway is induced by injuries to blood vessels.
Intrinsic clotting factors
The intrinsic pathway, which involves only factors within blood vessels, is thought to serve as a positive feedback loop, amplifying coagulation.
Fibrin formation
Fibrinogen is converted into fibrin though the use of thrombin
Three phases of coagulation cascade
Phase 1
Prothrombin activator
Phase 2
Prothrombin 3 and prothrombin activator become thrombin
Phase 3
Fibrinogen and thrombin become fibrin
Fibrin then also joins with thrombin to create a cross linked fibrin mesh
What happens to clots
Clots begin retracting within 30 minutes
Platelet growth factor stimulates fibroblasts and smooth muscle cells to multiply and repair damage.
Fibrinolysis terminates the clot
plasminogen helps dissolve fibrin helping break up clot
Blood clot dissolution cascade
Prekallikrein and factor X11 combine to form
Kallikrein
Kallikrein and plasminogen combine to form plasmin
Plasmin and fibrin polymer combine to degrade clots
Who did hematology begin with
Ancient Greece or ancient Egypt
Antoine Van Leeuwenhoek
Where do we find immature cells
Bone marrow biopsy
Bone marrow also contains fat cells
More fat as you get older
Where do we typically do a bone marrow biopsy
PSIS
Posterior superior Iliac Spine
Typically IO
Bone marrow calculation
100 minus age
example
a 30 year old is 100-30 = 70
they are expected to have 70% cells and 30% fat
Most useful tool in hematology
CBC
also most common lab in all of medicine
CBC components
RBC (Male - 4.3 -5.9, Female - 3.5-5.5 million)
WBC (4,500 -11,000) (also can be with Diff)
Hgb (Male - 13.5 - 17.5, female - 12.0 - 16.0)
Hct (Male - 41-53%, Female - 36-46%)
Plts (150,000 - 400,00)
Different values in pediatrics
RBC values
RBC
Male - 4.3 -5.9,
Female - 3.5-5.5 million
WBC values
WBC
4,500 -11,000) (also can be with Diff
Hgb Values
Hgb
Male - 13.5 - 17.5,
female - 12.0 - 16.0
decease during pregnancy
Hct Values
Hct
Male - 41-53%
Female - 36-46%
Platelet Values
Plts
(150,000 - 400,00)
decease during pregnancy
CBC short hand
Hgb
WBC Plt
Hct
What does hypervolemia do to CBC
All values will typically decrease due to excess water and more dilute blood.
When CBC is down, check patients volume status
(blood may be dilute)
What does Hypovolemia do to CBC
All values will typically increase due to decrease in water volume making the blood less dilute.
When CBC is up, check patients volume status
(blood may be very concentrated)
Low blood count name
-Cytopenias
High blood count name
-Cytoses or -philias
3 possibilities of cytopenia’s
Not producing enough blood cells
destroying blood cells
Losing blood cells
WBC with Diff
Monocyte Eosinophil basophil lymphocytes neutrophils
Neutrophils are most dominant and have greatest number (not in peds under 5, lymphocytes)
Neutrophils= bands+ segmented; AKA?
Neutrophils= bands+ segmented; also called polymorphonuclear neutrophils (PMNs,) polymorphonuclear leukocytes (PMLs), or granulocytes
Leukopenia causes (decreased WBC)
Medications (including chemotherapy and some antibiotics)
Viral infections
Leukemias, lymphomas, myelodysplastic syndrome
Aplastic anemia
Radiation exposure
Leukocytosis- Elevated WBC
Neutrophils: infection, inflammation, steroid effect, CML
“left shift” ≥ 10% neutrophil bands
Eosinophils: hypersensitivity reaction, parasitic infections, lymphomas (Hodgkin’s), myeloid leukemias
Basophils: hypersensitivity reaction, CML
Monocytes: viral infections (ie EBV, CMV), bacterial infections
Blasts: acute leukemias, myelofibrosis (Never normal)
Lymphocytes: EBV infection, Bordetella pertussis, CLL
“Atypical” lymphocytes: infection, inflammatory response, lymphomas
Hemachromatosis
Iron overload
Risk factors Hemoglobinopathies RBC malignancies, sideroblastic anemias, multiple transfusions
Liver is most affected by Iron overload
lethargy
Labs
serum ferritin level significantly elevated, transferrin saturation elevated, and liver enzymes elevated
Tx- iron chelation
Hereditary Hemochromotosis
Inherited form of iron overload
Due to mutation in HFE gene on chromosome 6; predominant in those of Northern European descent
Usually asymptomatic until age 40-60 years
Men > women
Same signs/symptoms, lab findings, & imaging findings as acquired form
Bronze tan looking skin
Treatment: phlebotomy (blood letting)
Thrombosis
The obstruction of blood flow due to formation of clot (thrombus)
Difference between arterial and venous blood clots
Arterial = (abnormal state of vessel wall, platelets) High flow areas white thrombus Coronary arteries (MI) Carotid arteries Cerebral arteries (stroke)
Venous = (defect in proteins, hypercoagulability) Low flow areas Red thrombus usually occlusive DVT PE
HIT
Heparin induced thrombocytopenia
Both arterial and venous clots
5-14 days after exposure
can be heparin or LMWH (lovenox)
can be a very small amount
Reduce the number of platelets while activating them
4 T's Thrombocytopenia Timing relative to heparin exposure Thrombosis Other
Can be confirmed by ELISA
Stop Heparin, no more heparin for life
Anti phospholipid syndrome
Both arterial and venous clots
Arterial clots
Arterial = (abnormal state of vessel wall, platelets) High flow areas white thrombus Coronary arteries (MI) Carotid arteries Cerebral arteries (stroke)
tx = antiplatelet therapies Aspirin Plavix (clopidogrel)
Venous clots
Venous = (defect in proteins, hypercoagulability) Low flow areas Red thrombus usually occlusive DVT PE
Tx =TPA
Virchow’s triad
Venous clots risk factors
Stasis of blood flow (usually immobility, long flights)
Endothelial injury (injury to vessel wall,{surgery, accident})
Hypercoagulability (Most are acquired, some hereditary)
Hypercoagulable states
Pregnancy, postpartum Antiphospholipid syndrome Surgery Estrogen use Cancer
Malignancy and Hypercoagulable states
20% of people with DVT have a malignancy
Trousseaus syndrome associated with multiple cancers
Causes multiple clots all over body
Surgery and Hypercoagulable states
Surgery and up to a month after can cause Hypercoagulable states
due to increase in cytokines and coagulation factors
can increase platelet count and reactivity
the longer and more invasive the surgery the more risk for venous blood clots
can be over 50% risk in some orthopedic surgeries (Hip, knee replacement,) and cardiothoracic surgeries
Pregnancy or exogenous estrogen and Hypercoagulable states
Exogenous estrogen can be birth control
Risk increases between 4 and 50 times that of non pregnant women.
Symptoms can be delayed due to symptoms mirroring those of pregnancy
Antiphospholipid syndrome and Hypercoagulable states
Autoimmune, can be associated with other autoimmune disorders such as Sjogren’s, SLE
Both arterial and venous thrombus
Can cause pregnancy complications such as fetal loss, preeclampsia, placental insufficiency
If multiple fetal losses, work up APLA, could be due clots
Also associated with thrombocytopenia (25%)
Thrombocytosis
High platelet count
over 450,000 fairly common (especially in surgery)
Risk of thromboses doesn’t increase until over 1 million
Venous thromboembolism
DVT
PE
DVT
Usually in lower extremity
Prone to venous stasis
Upper extremity DVT is usually associated with Medical device like a port or PICC line, pacemaker
DVT symptoms
Unilateral calf pain, cramping, swelling
Constant, progressive, redness
Unilateral unequal edema
positive Homans sign
DVT symptoms
Unilateral calf pain, cramping, swelling
Constant, progressive, redness
(can be similar to venous insufficient, cellulitis, etc.)
Unilateral unequal edema
positive Homans sign
Elevate D Dimer (>80%)
Definitive is Ultrasound with venous doppler
What is definitive for DVT
Ultrasound with venous doppler
If blood clot is present, vein wont compress
Diagnosis of PE
Almost always the result of DVT
Symptoms: dyspnea, pleuritic chest pain, cough, hemoptysis
Tachycardia is most common sign in PE
ekg changes S1Q3T3 sign
S waves in lead I, Q waves and inverted T in lead III
D Dimer (95%)
Chest x ray Usually normal. rarely can show Westermark’s sign or Hampton’s Hump
DX: CT angiogram with IV contrast
If cant get contrast use VQ Scan
EKG changes in PE
S1Q3T3 sign
S waves in lead I
Q waves in lead III
Inverted T wave in lead III
3 classifications of PE
Massive (high mortality) causes hypotension
Sub Massive (not in main pulmonary, low mortality rates, may be asymptomatic
Low risk
Criteria for PE workup
Wells (most common)
PERC (used in ED)
Gestalt
Geneva
Treatment for VTE/PE
Anticoagulation is mainstay of therapy
3 months for distal (smaller vein) DVT
3-6 months for PE, multi-vessel, or proximal DVT (larger vein)
Antiplatelet therapy (aspirin, clopidogrel)
Thrombolytics/fibrinolytics (tPA)
Clotting cascade blockers/ Anticoagulants
Anti-coags are used to prevent the progression and embolization of the clot not to break it down.
Anti coagulation meds for VTE/PE
Indirect Thrombin inhibitors (heparin, enoxaparin{lovenox}, fondaparinux{Arixtra})
Direct Thrombin Inhibitors (dabigatran{pradaxa})
Direct Factor Xa Inhibitors/DOACs (rivaroxaban{xarelto}, apixaban{eliguis})
Vitamin K antagonists (warfarin)
Anticoagulation for treatment of VTE
Varies by extent of VTE, patient’s co-morbidities/other medications, & availability of reversal agents
- Oral anticoagulant monotherapy with rivaroxaban (Xarelto®) or apixaban (Eliquis®). No parenteral anticoagulant used. [small or asymptomatic/outpatient]
- Start parenteral* anticoagulant then “bridge” to warfarin (Coumadin®){ED, need IV]
- Start parenteral anticoagulant x 5 days then switch on 6th day to oral anticoagulant such as dabigatran (Pradaxa®)
- Start parenteral anticoagulant and continue. No oral anticoagulant used. (most symptomatic patients)
Why does warfarin require a bridge
Decreases likelihood of skin necrosis
Takes a few days to 5-10 to take effect
INR goal in VTE/PE
between 2-3
INR is based on goals
Heparin monitoring
PTT
60-80
Anti 10a levels are more preferred way
Absolute contraindications to anticoagulation
Active bleeding Major trauma Recent or planned high risk surgery Severe bleeding diathesis (as with liver failure) Intracranial hemorrhage
IVC Filters
If anticoagulation is contraindicated in patient with VTE, consider an Inferior Vena Cava filter
Prevents emboli to lungs (PE)
Temporary
Little fingers catch DVTS so they cant reach lungs
Can cause vascular injury which can promote DVT
Treatment of Severe VTE
Rarely done
Fibrinolysis (ie IV tissue plasminogen activator) TPA
Pharmaco-mechanical thrombolysis (catheter-directed)
Surgical embolectomy (no longer done)
Superficial Venous Thrombosis/ Thrombophlebitis
Presents with erythema, tenderness, and palpable “cord”
Does not require systemic treatment, self-limited
Warm compresses may alleviate discomfort
Most common cause is IV insertion
What are inherited hypercoagulability also called
Thrombophilia
inherited hypercoagulability
may require life long anti coagulation therapy
usually under 40
family history
pregnancy issues
Leiden factor V (most common) (special gene test)
Protein C & S Deficiencies
Antithrombin III Deficiency (rare)(heparin resistant)
Are arterial or venous thromboses the major cause of morbidity and mortality
Both arterial and venous thromboses are a major cause of morbidity and mortality
Multiple VTE with no clear hypercoagulable state
Multiple VTE with no clear hypercoagulable state should trigger a workup for inherited thrombophilias
Anti coagulant drug of choice for renal issues
Warfarin
How long are red blood cells in circulation?
2 days
7-10 days
30 days
120 days
120 days
What is the treatment of choice for hereditary hemochromatosis?
Iron chelation therapy
Warfarin
Phlebotomy
Aspirin
Phlebotomy
Which one is characteristic of a venous thrombosis
Occlusive
Platelet rich
Occur in coronary and cerebral vessels
Dependent on state of vessel wall
Occlusive
Virchow’s triad include hypercoagulability, endothelial injury and___________?
Thrombophilia
Coagulopathy
Venous Stasis
Cardiomyopathy
Venous stasis
What are 3 things in Virchow’s triad
Venous stasis
Hypercoagulopathy
Endothelial injury
Which lab test for a fibrin split product and is highly sensitive for the presence of PE or DVT?
Fibrinogen
PTT
D Dimer
PT/INR
D-Dimer
What causes a false positive on D dimer
Pregnancy
age over 70
Which of the following is an absolute contraindication to anticoagulation therapy?
Platelet count of less than 50,000
INR> 1.5
Active bleeding ulcer
Frail / elderly patient
Active bleeding Ulcer
Hemostasis Steps
Platelet plug (antiplatelet therapy inhibits)
Adhesion, aggregation, activation, stabilization
Ex. Plavix, aspirin
Fibrin clot (anticoagulants inhibit)
Coagulation cascade
Ex. Heparin, Warfarin
Fibrinolysis (antifibrinolytics inhibit)
Fibrin clot degradation
Ex. TXA
Tissue repair
First 3 steps take 5 minutes (avg)
How long do the first 3 steps of hemostasis take?
5 minutes
Differnece between primary and secondary bleeding disorder
Primary is platelet problem
Platelets are less than 50,000
Secondary is a clotting disorder
(clotting factor)
Signs of primary bleeding disorder
Primary is platelet problem
Platelets are less than 50,000
Petechiae Purpura ecchymoses Hematomas Oral bleeding (gums) Epistaxis Hematuria GI bleed Menorrhagia (7days total or 3 days heavy flow)
Signs of secondary bleeding disorder
Secondary is a clotting disorder
(clotting factor)
Hemarthrosis Intramuscular hematomas (psoas muscle) Intracranial hemorrhage Severe GI Bleed Deep Hemorrhages
Are petechiae blanchable?
non blanchable
What is purpura?
the patch version petechiae
Non blanchable
Labs to draw in bleeding or unusual bleeding
CBC
tells you platelets and whether they are anemic
Coags
PTT (intrinsic pathway)
PT (extrinsic pathway)
INR (PT and INR are almost always reported together
Secondary tests Thrombin time (clotting time) Fibrinogen LFT Blood Smear Platelet function test (bleed time) Von Willebrand Mixing studies
(can also test for each individual clotting factor)
Thrombocytopenia
Platelet disorder
Platelets are too low
platelets under 140,00 (140,00-450,00)
Clinically significant if under 100,000
Under 50,000 (at risk for severe post traumatic bleed)
Can be very small trauma such as bump on head
Under 10,000 (risk for spontaneous bleed)
Gets transfusion
3 reasons platelets might be low
Platelets are being lost
Platelets are being destroyed
Platelets are not being made
HHIT SHOCK
HIT
HUS
ITP
TTP
Splenomegaly Hereditary Other Chemo Kasabach Merritt syndrome
Other includes=
Bone marrow, SLE, alcoholism, Malignancy, DIC sepsis, Viral, meds
Thrombocytopenia due to Systemic Disorders
Sepsis/ infections: HIV, EBV, HepC, CMV, rubella, mumps, varicella, malaria, dengue fever, Rickettsiosis , H. pylori
Pregnancy & post-partum
Malignancy
Alcoholism
Systemic Lupus Erythematosus
Vitamin B12, iron, or folate deficiency
Immune/Idiopathic Thrombocytopenic Purpura (ITP)
Autoimmune disorder with IgG antibodies against platelets (macrophages destroy platelets)
Affects both children and adults
(Kids usually self limiting, adults usually chronic)
Has same Signs/symptoms of thrombocytopenia
Appear healthy and well otherwise (feel fine)
Laboratory exams: Platelet count <50k, no anemia or leukopenia, enlarged platelets on peripheral smear, normal coagulation studies.
Normal RBC, WBC (only platelets affected)
Platelet-associated IgG antibody assay available
Testing not very specific
Diagnosis of exclusion
ITP Treatment
If platelets are below 30,000 give treatment
Glucocorticoids are first line (prednisone 1mg/kg 1wk)
IVIG, Anti-Rho GAM, transfusion if bleeding
Usually respond within 3-5 days
second line is (typically for adults/chronic)
thrombopoietin receptor agonists, rituximab, immunosuppressive therapy, splenectomy for relapses
Thrombotic Thrombocytopenic Purpura/ Hemolytic Uremic Syndrome (TTP/HUS)
Microangiopathy due to antibodies to ADAMTS13,
pregnancy, malignancy, HIV, drugs (quinine), infection
In kids usually shigella or E.coli infection
Pentad of features: 1. Thrombocytopenia, 2. Hemolytic anemia, 3. Fever, 4. Renal insufficiency, 5. Neurological deficits (headache, somnolence, delirium, seizures, paresis, or coma)
TTP and HUS are different
Medical emergency due to ischemic multi-organ failure
Thrombotic Thrombocytopenic Purpura/ Hemolytic Uremic Syndrome (TTP/HUS)
Features
Pentad of features:
- Thrombocytopenia, (less than 20,000)
- Hemolytic anemia,
- Fever,
- Renal insufficiency,
- Neurological deficits (headache, somnolence, delirium, seizures, paresis, or coma)
Difference between
Thrombotic Thrombocytopenic Purpura
and
Hemolytic Uremic Syndrome (TTP/HUS)
ADAMTS13 assay indicates TTP
Thrombotic Thrombocytopenic Purpura/ Hemolytic Uremic Syndrome (TTP/HUS)
Treatments
Treatments: emergent plasma exchange if TTP >HUS, eculizumab if HUS>TTP, RBC transfusions, hemodialysis, IVIG, corticosteroids, rituximab, cyclophosphamide, splenectomy
4 T’s of HIT
4 T's Thrombocytopenia Timing relative to heparin exposure Thrombosis Other
Can be clotting and bleeding at same time
Inadequate antibodies PF4 (Platelet factor 4)
Hemolysis, Elevated Liver enzymes, and Low Platelet (HELLP) Syndrome
Pregnant disorder
Peri-partum disorder (3rd trimester) on eclampsia spectrum
Present with High BP and proteinuria
Low platelet
High Liver enzymes
Hemolysis (RBC fragments on smear)
Risk of hepatic hemorrhage (RUQ Pain)
Placental abruption
TX: prompt delivery, RBC’s, platelets, Mag sulfate, antihypertensives
What is platelet clumping considered
Pseudo Thrombotic Thrombocytopenic Purpura (TTP)
First step for any thrombocytopenia
Examine peripheral blood smear
Persistent thrombocytopenia, no clear etiology, over 60 years old
Bone marrow biopsy for cancer rule out
Qualitative Platelet Disorders
normal number of platelets but they aren’t functioning properly
Von Willebrand’s Disease Drug induced Uremic platelet dysfunction due to renal failure Liver failure Cardiac bypass Inherited
Von Willebrand’s disease
1% of population Mild to severe Inherited History of bleeding Acquired form (rare) Special test just for it (RIPA)
Prolonged PTT, normal PT, normal platelet count
TX:
Desmopressin
Aminocaproic acid
TXA
PFA 100
Tests platelet function and aggregation
Pro clotting meds
Desmopressin
Aminocaproic acid
TXA
Drugs that decrease platelet function
NSAIDs, aspirin, & clopidogrel (Plavix®)
NSAIDs and aspirin inhibit COX-1
Also avoid in preoperative period & if already on anticoagulants or SSRIs
Selective Cox 2 (Celebrex) doesn’t inhibit platelet function
Hold for 7-10 days prior to surgery
Coagulopathy
Pro bleeding
Labs to always get on bleeding patient
CBC
Coags
Abnormal Coag studies
PT prolonged, PTT normal: Factor VII
PT normal, PTT prolonged: Factors VIII, IX, XI, XII
Both PT & PTT prolonged: Factors V, X
Hemoaphilia
X linked, more prominent in males Type A (factor 8) deficiency Type B (factor 9) is also called Christmas disease
Severe bleeding -
Spontaneous hemarthrosis, muscle hematomas, GI bleeds, circumcisions
Labs: Prolonged PTT with normal PT; Factor 8 or 9 assay is diagnostic.
***Mixing study required to rule out clotting factor inhibitors.
TX: factor infusions, TXA, avoid trauma/contact sports
Vitamin K deficiency
Dark green leafy veggies
Most often due to malnutrition or fat malabsorption (ie Celiac’s) (not just low vegetables)
superficial bleeding & easy bruisability to severe bleeds
PT/INR is prolonged, PTT also prolonged if severe
Treat underlying cause, give vitamin K
Also associated with anaphylaxis, must be given under supervision
Liver Failure Associated Coagulopathy
Liver makes thrombopoietin, prothrombin, fibrinogen
Thrombopoietin makes platelets, if you have liver failure this can cause increased bleeding.(significant liver failure)
factor V deficiency indicates liver failure over vitamin K deficiency
Tx: Administer fresh frozen plasma if bleeding
FFP has all the coag factors in it
Disseminated Intravascular Coagulopathy (DIC)
Worst Coag Disease
80% mortality rate
Medical emergency
Labs: , low fibrinogen, Prolonged PT and PTT, platelet count <100k elevated D-dimer, elevated fibrin split products
**Very few things give low fibrinogen (DIC)**
platelet transfusion if bleeding predominates,
tissue plasminogen activator (TPA) if clots predominate
Causes:
Septic shock
Obstetrical complications
Cancer
1:1 mixing study
take impaired clotting blood,
mix it with good blood
and see if the coagulation improves
If it improves person was deficient in clotting factor
Clotting factor inhibitors
anti-factor-8
high incidence with hemophilia (rare otherwise)
1:1 mixing study
Bleeding disorders occur as a result of?
Platelet
or
Coagulation factor
deficiencies
Bleeding due to primary hemostasis/platelet disorder is usually more
superficial or less severe than secondary hemostasis/coagulation factor disorders
A platelet count under 100 is?
clinically significant
and warrants work up
Thrombocytopenia most commonly occurs due to?
Medications or
secondary illness
but can occur due to ITP, TTP/HUS, HIT, DIC, HELLP
If platelet count and coag studies are normal and patient is still bleeding?
Need to rule out
qualitative platelet disorder
(Von Willebrand disease)
Coagulopathies include?
Hemophilia Liver failure Vitamin K deficiency DIC HELLP
Anemia defenition
Low
Hgb (amount of hemoglobin)
Hct (volume/percent of RBC in blood)
RBC count (number of red blood cells)
Can be called anemic based on CBC values
3 causes of anemia
being destroyed
not being produced
being lost
Causes of anemia where RBC are being destroyed
Hemolysis:
Autoimmune G6PD PNH (Paroxysmal nocturnal hemoglobinuria) TTP/HUS Infections Thalassemia Sickle cell Hypersplenism
Causes of anemia where RBC are being lost
Acute
Chronic
Hypersplenism / splenic sequestration
Causes of anemia where RBC are not being produced
Hypoproliferative( produced in too few numbers)
-Iron deficiency
-Folic acid deficiency
-Vitamin B12 deficiency
-Renal failure
-Anemia of chronic disease
-Hypothyroidism/-gonadism
-Bone marrow suppression or failure (malignancy,
medications, aplastic anemia)
Ineffective or unstable erythropoiesis (ineffective)
- Sickle cell anemia - Thalassemias - Sideroblastic - Methoglobinemia
3 main classes of anemia
Microcytic
Normocytic
Macrocytic (megaloblastic or non megaloblastic)
Megaloblastic anemia vs non megaloblastic anemia
Megaloblastic
Abnormal nuclear maturation of RBC
Non-megaloblastic
Lots of immature RBC (reticulocytes)
Microcytic anemia causes
TICS
Thalassemia
Iron deficiency
Chronic disease
Sideroblastic anemia
Macrocytic megaloblastic anemia causes
Folate deficiency
Vitamin b12 deficiency
Macrocytic non-megaloblastic anemia causes
Liver disease
alcoholism
Reticulocytosis
Drugs
What are reticulocytes
Immature red blood cells
Larger than normal red blood cells
Can order a reticulocyte count or RPI
(represents bone marrow response to anemia, most often in hemolysis or bleeding)
RBC indices (on CBC)
MCV = Mean corpuscular volume MCHC = Mean corpuscular hemoglobin concentration MCH = Mean corpuscular Hemoglobin RDW = RBC distribution width
MCV
Mean corpuscular volume
(on CBC)
Average red blood cell size
<80 is microcytic
80-100 is normal
>100 is macrocytic
MCHC
Mean corpuscular hemoglobin concentration
Average RBC concentration of hemoglobin
(on CBC)
<32 = hypochromic (undersaturated)
32-37 normal
>37 = Hyperchromic (oversaturated)
MCH
Mean corpuscular hemoglobin
Average hemoglobin per red blood cell
(on CBC)
Volume not taken into account, MCHC is better measurement
RDW
RBC distribution width
Measures variation in red blood cell size
(on CBC)
anistocytosis = variation in size of RBC Poikilocytosis = variation in shape (only on smear)
What is basophilic stippling associated with
Lead Poisoning
What does lead poisoning show on a blood smear
Basophilic stippling
Labs to consider for anemia
CBC
Others to consider
Iron study Folate levels B12 Levels Full hemolysis workup Occult stool
Anemia approach to diagnosis
are they really anemic? Lab error, hypervolemic
Is it acute or chronic?
Symptomatic or asymptomatic?
(Acute is usually symptomatic, chronic not always)
Are they hemodynamically unstable?
Blood loss?
Age, sex, pregnant, menses?
Meds, infections, family history, substance use, Gi, diet
Affects of anemia
Fatigue (especially if hgb <10)
Pallor (oral mucosa and conjunctiva)
Dyspnea
Systolic murmur (reverses when anemia is corrected)
Hypoproliferative anemias
Iron, b12 folate deficiency
5 reasons for vitamin/mineral deficiency
inadequate intake malabsorption increased utilization or loss drug inhibition genetic defect
Most common anemia world wide
Iron deficient anemia
Iron deficient anemia
almost always due to bleeding rarely nutrition (3rd world)
Premenopausal women
pregnant women
adolescents
In adult men and post menopausal women
look for bleeding
PICA, spoon nails, dysphasia, Cheilosis
Crohns, celiacs
Typically microcytic (iron tell RBC to stop shrinking)
elevated transferrin
low iron and transferritin, ferritin
TX: cause, replace iron PO then IV
slight risk of anaphylaxis in IV iron
Which of the following is sign of a secondary hemostasis disorder?
Petechia
Hemarthrosis
Epistaxis
Ecchymosis
Hemarthrosis
What is a secondary hemostasis disorder
A clotting factor problem not a platelet problem
Platelet bleeding is usually more superficial
and clotting factor problem is usually a deeper bleeding
Thrombocytopenia becomes clinically significant when the platelet count is less than?
100,000
Begin workup
Normal is 140 - 450
Which of the following conditions is associated with E.coli 0157:h7 infection? especially in children?
ITP
Hemophilia
TTP
HUS
HUS
Which of the following is a cause of thrombocytopenia mediated by antibodies to PF4 and associated with increased risk of thrombosis?
TTP
DIC
HELLP
HIT
HIT
Heparin induced thrombocytopenia
Antibodies to platelet factor 4 (PF4)
(All of these cause thrombocytopenia)
In the US iron deficiency is most often due to which of the following
Inadequate intake malabsorption increased utilization or loss drug effects genetic defects
Increased utilization or loss
Bleeding is most common in US
Megaloblastic anemia
B12 deficiency
Megaloblastic (macrocytic)
Abnormal nuclear maturation of RBC
B12 deficiency - B12 ingested, binds to intrinsic factor in stomach and is absorbed in the ileum, then transported into circulation by trans coalamin.
b12 essential for myelination of nervous system
B12 only found in foods of animal origin
usually due to absorption issue (celiacs, crohns)
Also post gastric/bariatric surgery. vegans. H. pylori
Smooth beefy red tongue
Peripheral neuropathy (common), balance, GI, AMS, weight loss, anorexia
Labs: low b12 level, macrocytic, high RDW,
Give B12 injections (due to absorption issues)
Can give PO if not absorption
resolves in 2 months, if chronic, lifelong tx.
Pernicious anemia
Sub class of b12 deficiency (megaloblastic anemia)
Low production of intrinsic factor which helps absorb b12
gastric bypass patients,
gastric atrophy in older people
Diagnosed by schilling test
(measures ability to absorb b12)
Tx: same as b12 deficiency
increased risk of gastric cancers
Megaloblastic anemia
Folic acid deficiency
Very often occur together with b12 deficiency
folic acid is absorbed in the jejunum
requires b12 to enter the cells
leafy greens, liver, fruits, nuts
risk: malnourished (alcoholics)
geriatric, cancer patients
Meds that inhibit folic acid = bactrim, phenytoin, methotrexate (give with supplement)
Pregnancy, dialysis
Labs:Labs: low folate level, macrocytic, high RDW,
give folate
Sideroblastic anemia
Microcytic
due to ineffective erythropoiesis
has all components for RBC but iron is not correctly incorporated into the red blood cell
Creates ringed sideroblasts (iron around RBC)
B6 deficiency, lead poisoning, myelodysplastic syndrome, copper deficiency, alcohol(usually macro), drugs, hereditary(very rare)
may cause hemochromatosis
treat cause
Anemia of chronic kidney disease
kidney failure
cause low production of EPO
Normocytic, Low epo levels
Give EPO until anemia corrects
Where are erythropoietin and thrombopoietin made?
erythropoietin is made in kidneys
Signal to bone marrow to make RBC’s
thrombopoietin is made in liver
Anemia of chronic disease
or
Anemia of chronic inflammation
Caused by increase in proinflammatory cytokines which decrease erythropiesis
TTULAC
Thyroid, TB, UTI, Liver, Auto immune, cancers
Normocytic or microcytic
**Ferritin is elevated with inflammation***
Ferritin is elevated in response to inflammation just like CRP or ESR
Treat cause (no specific tx) (could eventually need transfusion) can benefit from EPO injections
Usually macrocytic if alcohol is involved
Aplastic anemia
Aplastic pancytopenia
Bone marrow failure resulting form damage to hematopoietic stem cells
Bone marrow failure
Not making any cells
Dx: bone marrow biopsy
65% are idiopathic
Autoimmune, chemo, toxin, drug, virus, radiation poison
Drugs, bone marrow transfusion
Hemolytic anemias
bone marrow is making RBC’s but they are destroyed
jaundice, splenomegaly
Splenic sequestration
enlarged spleen due to too many RBC’s and fragments
Splenic resection, splenectomy
Labs: High MCV, RDW, Low hgb, high reticulocytes, high bilirubin, low haptoglobin, high LDH,
Fragments on smear
hemoglobinuria
Direct coombs test / antiglobulin test if positive autoimmune, drug, transfusion, infection or cancer if negative g6pd, PNH, TTP/HUS or DIC
First clues are physical exam and macrocytic anemia
then order other labs
2 classes of hemolytic anemia
intrinsic
Many types
Vigorous exercise, self correcting
extrinsic many types Parvo virus(slapped cheek) (self limiting)
AIHA
Auto immune hemolytic anemia
Caused by IgG or IgM antibodies attacking RBC’s
50% idiopathic
Autoimmune, malignancies, drugs
10% also have ITP (called Evans syndrome)
(antibodies against platelets) (poor prognosis)
Labs: hemolysis, +direct coombs test
Tx: SPIR
Splenectomy, rituximab, IVIG, prednisone
G6PD deficiency
inherited, X linked, Black males
can affect anybody
decreased ability of RBC’s to deal with oxidative stress
Fava beans, dapsone, Bactrim, Macrobid, primaquine, infections
Labs: Heinz bodies, fragments, hemolysis
G6PD enzyme assay
Asymptomatic whole life until they get one of these oxidative drugs that causes a stressor.
Tx: no specific treatment, avoid oxidative drugs
PNH
Paroxysmal Nocturnal hemoglobinuria
(not common) (inherited)
RBC’s have abnormal sensitivity to complement especially at night when the body is more acidic.
mostly in children,
hemoglobinuria worse in morning, improves throughout the day.
Dx: Flow cytometric assay which will be positive for CD55 and CD59
Tx: ecluzimab
Anemia due to blood loss
external or internal
Labs: low hgb/hct
Chronic=iron deficiency (microcytic)
Acute = Elevated reticulocytes (macrocytic)
(stage depends on CBC whether it is acute or chronic)
Severe acute bleed can have delay in hgb/hct
(will still have signs of hypovolemia)
What could a GI bleed show on labs
Aside from CBC
BUN could be high with a normal creatinine
Hemoglobinopathies
Disorder of globin synthesis or stability
leads to anemia
Common in malaria regions
i.e. thalassemia and sickle cell
Dx: hemoglobin electrophoresis (test)
Hemoglobin anatomy
Hemoglobin in a normal adult
Heme+4 globin units
(2 alpha chains, 2 beta chains)
Heme = iron + 4 protoporphyrins
99% Hgb A
1% Hgb B
almost no Hgb F
Hgb S is abnormal (s is for sickle)
Thalassemia
Inherited
(not producing enough alpha or beta chains)
results in in effect
Microcytic anemia
Normal RBC count, hemoglobin is just not effective
Dx: hemoglobin electrophoresis (test)
Globin gene test (most effective)
Shows target cells on smear
Very severe will have extramedullary hematopoiesis
Thalassemia Beta Major
Mediterranean, mid east, SE asia
Major = no beta chain hgb
Jaundice, pallor, failure to thrive
life long transfusion dependence & marrow transplant
Thalassemia Beta Intermedi
dx: ages 2-4
may be transfusion dependent
can require splenectomy
varies in severity
Thalassemia Beta Minor
Asymptomatic
carrier
may have very mild microcytosis or anemia
Thalassemia Alpha Major
Mediterranean, mid east, SE asia but also African
Major:
Not making alpha chains (only “hgb barts”)
Hydrops fetalis (death in utero)
Thalassemia Alpha intermedia
loss of three of four alpha chains
Also called HgH disease.
Usually not transfusion dependent, but will be anemic with Hgb 9-11 g/dL.
May have signs of chronic hemolysis and/or extramedullary hematopoiesis in spleen or liver.
Thalassemia Alpha minor
loss of two of four alpha chains.
Non-specific signs/symptoms of anemia.
Common with African ancestry.
Thalassemia Alpha minima
Loss of 2 of 4 alpha chains
Asian descent
not anemic but hypochromic
Chipmunk facies
Beta thalassemia major
or
undiagnosed Alpha thalassemia intermediate
When you see microcytic anemia
get iron studies
Thalassemia = normal
Iron deficiency = all low, high TIBC
Chronic disease = low everything, high ferritin
Sideroblastic = normal
Sickle cell
causes cells to sickle
poor oxygen capacity
very painful (hours to weeks)
organ ischemia and infarct
if more than 3 crises Q year = poor prognosis
Priapism, infarcts, organ failure, leg ulcers PVD
acute chest syndrome (fever, cough, hypxoemia, tachy)
behavioral
Labs: HbgS, normocytic/normochromic
granulocytosis
Avoid high altitude, cold, manual labor
Tx: hydroxyurea IV hydration Pain meds Transfusion Splenectomy + vaccines could need bone marrow transplant (can be curative)
Methmoglobinemia
Acquired
can be iatrogenic
abnormal form of hgb
Causes:
Nitrites, drugs, anesthesiology
Can be lethal
Tx: IV methylene Blue
5 types of hematological malignancies
Leukemias Lymphomas Multiple myeloma Myeloproliferative disorders Myelodysplastic syndromes
All are diagnosed by bone marrow biopsy or lymph node biopsy (gold standard)
Leukemia (acute)
Increase of blasts (precursor cells)
Very high WBC
Diff shows blasts
Causes anemia due to too many WBC’s in bone marrow
Bruising, bleeding, bone pain, infections
AML or ALL
Over 20% blasts is diagnostic of acute leukemia
Leukemia (acute)
AML
> 20% myeloblasts (normally less than 5)
Also on bone marrow biopsy
Auer rods = AML
Down syndrome, radiation, drugs, chemo, smoking
7+3 Chemo +/- marrow
Intermediate to high risk
palliative = hydroxyurea
Dx: molecular recited, genetic features
Leukemia (acute)
ALL
> 20% lymphoblasts (normally less than 5)
Also on bone marrow biopsy
Most common malignancy in children (3-5) 30% of all
High incidence of CNS involvement
Chemo, Marrow, CAR T cell therapy
Standard practice to do LP due to CNS involvement
Omaya resevoir
Port to CSF for ALL
Chronic Leukemia
Not all requires treatment
CML Chronic myelogenous leukemia
CLL Chronic lymphocytic leukemia
CML Chronic myelogenous leukemia
Malignancy of mature granulocytes
Really high WBC
usually dx 55-65
can be asymptomatic, fatigue, fever, splenomegaly
Caused by translocation of chromosome 9 & 22
Philadelphia Chromosome (BCR-ABL gene)
Bone marrow biopsy to confirm
Blasts will not be over 20%
TKI Gleevec
CLL Chronic Lymphocytic Leukemia
Lymphoid cells
Age of onset 70
WBC over 20,000
can be asymptomatic, fatigue, splenomegaly
Dx: peripheral Blood flow cytometry
Bone marrow biopsy
Lymph biopsy
Smudge cells on smear
Prone to ITP, Hemolytic anemia
Might be genetic (only blood cancer)
Tx: BTK, rituximab, chemo
Lymphomas
Cancer of Mature B lymphocytes
Usually B cells
Rare = T or NK cells
Hodgkins and non hodgkins
S/S = lymphadenopathy, hepatosplenomegaly
B symptoms = Fevers, drenching night sweats, unintentional weight loss >10% in 6 months
Check lymph nodes May have lymphocytosis, + LDH, hypercalcemia Associated EBV, HIV Pet scan Biopsy required to confirm
B cell cancer, big lymph/liver/spleen, pet scan
drenching night sweats*
Lymph nodes with lymphoma
non tender / painless Fixed Firm / hard >2cm >2 weeks unilateral unusual locations
Hodgkins lymphoma
B cell lymphoma
Reed sternberg cells in biopsy
age 20-30 or over 60
more in males
Painless lymphadenopathy above the waist
Painful with alcohol
Tx: ABVD +/- radiation
Considered pretty curable
Non-hodgkins lymphoma
10 times more common than hodgkins
all other lymphomas
R CHOP, marrow, CAR T cell
Diffuse large B cell is most common type
MALT (H.pylori)
Others
Multiple myeloma
Cancer of plasma cells (most mature B cells)
CRAB
Hypercalcemia, - Renal, Anemia, Bone lesions
lytic bone lesions
Age around 67
M spike is special test in serum or urine
High protein on smear Rouleaux formation (stacking of RBC's)
RVD, Marrow, radiation, kyphoplasty
30% of periosteum must be gone for lytic lesions
Waldenstroms Macroglobulinemia
Malignancy of lymphoplasmacytic cells that secret IgM
Low blood counts (cytopenias) +protein, abnormal coag tests
Usually kinda sick
S/S= lots splenomegaly, reynauds, weak, weight loss, fever, purpura
**Hyperviscosity syndrome*
Tx: early observation
Late = chemo, marrow
Amyloidosis
Not a cancer
Protein misfolding disorder
Affects the organs
****big tongue, raccoon eyes
Amyloid protein deposits, Congo red stains
Can be fatal
TX similar to Multiple myeloma
Myelodysplastcic syndrome
Pre cancerous syndrome
Can evolve into AML
Over 60
idopathic
gradually worsening cytopenia
<20% blasts
Sideroblastic
Ringed sideroblasts on smear
observation, hypomethylating, immunomodulators
Mild = observation
more severe = chemo +/- marrow
Myeloproliferative Disorder/neoplasms
overproduction of myeloid cells (RBC, platelets, granulocytes)
**Mutation of JAK-2**
Can evolve into AML
**Massive splenomegaly**
female predominant
Polycythemia Vera
Hgb over 15
Rule out other causes of high hgb (smoking, epo use, dehydration, RCC, altitude, COPD etc)
**Serum EPO will be low****
Headaches, tinnitus, blurred vision, fatigue, hypertension, erythema
**pruritis with warm shower*******
Risk of death from thrombosis
Tx: Phlebotomy, hydroxyurea, ruxolitinib
Essential thrombocythemia
Too many platelets >1 million Rule out other high platelet causes usually asymptomatic bone marrow biopsy required for DX
Tx: Observation, ASA, hydroxyurea, ruxolitinib
Primary myelofibrosis
People are sick
poor prognosis
Too many stem cells
fibrosis of bone marrow
Teardrop RBC’c*
Unintentional weight loss
**massive splenomegaly**
Male dominant
over 60
Bone marrow biopsy, shows fibrosis
Treatment: ruxolitinib, prednisone+thalolidomide, INF-α, +/- allogeneic bone marrow transplant
Myelodysplastic syndromes
VS
Myeloproliferative neoplasms
Myelodysplastic syndromes are disorders of underproduction
Myeloproliferative neoplasms are disorders of overproduction
Misc. hematological malignancy info
Hematological malignancies and related disorders may present with cytoses or cytopenias on complete blood count
A peripheral blood smear may reveal abnormalities characteristic of a blood cancer
Lymphomas present with “B symptoms”, hepatosplenomegaly, and large, firm, fixed, & nontender lymphadenopathy
Acute leukemias present with sudden, significant symptoms and cytopenias with blasts >20%
Multiple myeloma presents with CRAB criteria and M-spike
Chronic leukemias, MDS, and MPNs are often found incidentally on routine CBC
When suspicion is high, tissue biopsy (typically bone marrow or lymph node) is needed to rule in/out a hematological malignancy
Oncological emergencies
Hyperleukocytosis/leukostasis Hyperviscosity syndrome Tumor lysis syndrome Neutropenic fever/Sepsis Superior vena cava syndrome
Neutropenic fever / sepsis
Neutrophils <1000 (severe is <500) on diff
Single temp over 101 or sustained (1hr) over 100.4
people receiving chemo
only symptom
Labs: cultures, urine, chest xray, lactic acid, procalcitonin if hypotensive
+gram cocci (ports), - gram rods, fungus, tb
Emergency, immediate broad spectrum AB, admit
only 30% of the time you find the cause
Hyperleukocytosis/leukostasis
Blast crisis
patients with acute leukemia
AML,ALL
WBC>50 mostly blasts
hypervisosity syndrome
Emergent hospital admittance for plasmapheresis
Tumor lysis syndrome
Massive tumor cell lysis releasing all teh toxins into the blood
Large amounts of phosphorus, potassium, and nucleic acids
people with lots of cancer
usually iatrogenic after cancer treatment
High uric acid, phosphorus, = AKI
High potassium = arrhythmia or arrest
Low calcium = seizures tetany
allopurinol or IV hydration prophylaxis
admit, telemetry, correct electrolytes, iv hydration, possible dialysis
patients feel sick
Hyperviscosity Syndrome
Waldenstroms macroglobinemia
Headache, blurred vision, altered mentation, stroke, paresis
Labs: serum viscosity
Emergent hospital admittance for plasmapheresis
SVC Syndrome
Superior vena cava syndrome
Compression of blood flow in SVC by tumor
lung cancer
Face neck swelling, chest pain, dyspnea,
Swollen from the neck up
Chest xray, superior vena cava gram is gold standard
Tx: reduce tumor
Types of blood products
Whole blood Packed RBC's Platelets FFP Cryoprecipitate
Apheresis
When blood is donated only one component is taken out and the rest is given back to the donor
(i.e. plasma)
Most common blood type
O positive (40%)
Least common blood type
AB neg (0.5%)
universal donor (blood)
O neg
Universal recipient (blood)
AB pos
RH factor
antigen D
80% are positive
Sensitization (alloimmunization) may occur from transfusions or pregnancy
Rh negative mother is exposed to Rh positive antigens and develops antibodies. So, subsequent pregnancies at risk for erythroblastosis fetalis at time of delivery.
Rh immunoglobulin, ie Rhogam®, is given to Rh neg mothers with Rh pos fetus
Transfusion decision criteria
Labs, clinical S/S, disease or goals
Not just lab values
Main goal of RBC transfusion
Establish adequate O2 carrying capacity
Main goal of Platelet transfusion
Stop or prevent bleeding
Hemoglobin rock bottom
Hemoglobin<7
Should never go below this
give blood
Platelet rock bottom
Platelets should never be allowed to go less than 10
give platelets
What to give FFP or cryo for
need coagulation factors
DIC
HELLP
Etc.
Options for pre-transfusion testing of patient:
Type and hold = wish list (unlikely will need)
Type and screen = layaway (might need in near future)
good for 72 hours
Type and cross = already bought clothes (patient definitely going to need blood)(only for this patient)
Trauma blood = immediate transfusion, doesn’t matter
Mostly for RBC’s
How much will 1 unit of of RBC’s raise Hgb?
1g/dl
lasts up to 42 days
How much will 1 unit of of platelets (pack) raise Hgb?
5000 - 10,000 (over 15mins)
1 pack of platelets = 4-6 units of platelets
Washed RBC’s
reduce anaphylaxis
decreases WBC’s
FFP
Fresh frozen plasma
lasts 1-7 years
coagulation factors
given for bleeding
once thawed use within 24 hours
increases coags by about 5%
Must be ABO compatible
Cryo
Cryoprecipitate
Concentrated fibrinogen
Very good for DIC
Transfusion reactions
most are immunological
immediate = <24 hours
or delayed >24hours
Typically to RBC’s, Platelets, or whole blood
Around 5% there is some kind of reaction
most occur within15 mins
most are not life threatening
**Stop transfusion****
Hemolytic transfusion reaction
Human error
Person given wrong blood type
Life threatening
Jaundice, headache, palpitations, respiratory distress, fever, shock
Labs: Hgb will be even lower due to RBC’s destroying each other
+direct coombs, fragments on smear
Tx: stop transfusion, IV resuscitation, steroids, pressors
Febrile nonhemolytic reaction
Most common type of transfusion reaction
Fever over 38 or +1 over baseline
Fever/chills without hemolysis, organ failure or shock
more transfusions, more risk (due to antibody buildup)
Tylenol
Allergic reaction (transfusion)
Most are mild: urticaria, pruritis, flushing
Due to antibodies
stop transfusion, Benadryl
Anaphylaxis is very rare
Benadryl, steroids, epi
Mast cell mediated
TRALI
Transfusion related acute lung injury
Due to antibodies
Patient will be sick
Dyspnea, SOB Fever, hypotension
Chest xray = bilateral pulmonary edema
Stop transfusion, supportive care (O2, diuretics)
Match platelets in future (HLA)
Premedication for transfusion reaction
It is done but is not evidence based
Delayed hemolytic reaction
Occurs 2-14 days after transfusion
unexplained fall of Hct/Hgb
S/S of hemolysis
+direct coombs,
usually no treatment required
Alloimmunization
Sensitization to RBC antigen with first transfusion, then reaction with second transfusion
Primary immunization occurs days or weeks post transfusion or pregnancy (mother develops antibodies to fetal RBC antigens) and asymptomatic
With subsequent transfusions, patient may have fever/chills
RBC or platelet antibody screen will be positive
no treatment, find appropriate donor
Graft versus host disease
due to left over things in RBC’s
T cells from donor attack bone marrow
very rare, possibly fatal
Rash, diarrhea, +liver enzymes
Non immunological delayed transfusion reaction
TACO
Transfusion Related Circulatory Overload
Pulm edema within 6 hours
Dyspnea, peripheral edema,
Elevated systolic BP**
Difference between TACO and TRALI
TRALI is immune mediated and TACO is not
With TACO, no fever and elevated BP
With TRALI Fever and low BP
Usually occurs in people that are already volume overloaded, anasarca, peripheral edema
Treat for volume overload
diuretics
Labs BNP will be elevated
Non immunological delayed transfusion reaction
Transmission of infectious disease
All blood products tested for Hep B/C, HIV, Syphilis, & other pathogens
Bacterial contamination in blood processing may occur
Patient will present with signs/symptoms of sepsis hours after transfusion: fever, hypotension
(like septic shock)
Clinically similar to hemolytic reaction, but no signs of hemolysis
Culture patient and blood product
Lactic acid may be elevated
Requires broad spectrum antibiotics
May require vasopressors
Non immunological delayed transfusion reaction
Hypothermia
Highest risk with refrigerated or room temperature blood products given at rapid rates
If high infusion rates are planned, a warming device is recommended
Patient may have chills, but hypothermic (temperature ≤35°C) instead of febrile upon temperature check
warm patient
Non immunological delayed transfusion reaction
Metabolic Disturbances/Electrolyte Toxicity
Higher risk with multiple transfusions in a short period
Hyperkalemia: K+ leaks out of RBCs; concerning if renal insufficient
Acidosis: due to sodium citrate (anticoagulant in blood products). For patients with liver disease, not metabolized quickly enough and lactate produced.
Hypocalcemia: also due to sodium citrate, as it binds to calcium
Iron overload/hemochromatosis: about 200mg of Fe per unit pf pRBCs, accumulates and deposits in organs (liver, heart, endocrine).
May require iron chelation medication.
What is cancer
diseases that have unrestrained cellular growth
Hallmarks of cancer cells:
Resisting apoptosis/cell death Sustaining proliferative signaling Evading growth suppressors (immune system) Activating invasion and metastasis Enabling replicative immortality inducing angiogenesis
Carcinogenesis
Multi step process
tissue and cellular changes
mutation of tumor suppressor genes or oncogenes
Cancer general risk factors
Older age Sex (M>F) race Inherited Toxins Radiation Pathogens (EBV, Hep b, H. pylori, HPV, etc)
Gold standard of cancer Dx:
Tissue sample (always need a biopsy) Pap FNA marrow lymph
Cancer staging
Many different staging types
most common is TNM
Number 1 cause of death in cancer patients
Infection
Why are cancer patients at high risk for infection?
Malnutrition
immune deficiencies
breakdown of epithelial barriers
Bacteremia
Cachexia
Weight loss
muscle loss
wasting syndrome
Requires intervention if over 10%
Paraneoplastic syndrome
Tumor is able to produce hormones
i.e. ADH, ACTH, PTH, EPO, etc.
Oncology branches
Medical oncology
(meds, chemo, antibodies, marrow)(given in cycles)
Immunotherapy
Surgical oncology
Radiation oncology
Goals of cancer therapy
Palliative vs curative
Determine how frail or robust is this patient, how much therapy can they get
Bone marrow transplant
Hematopoietic stem cell transplants
Basically give the patient a whole new immune system
most often for hematological malignancies
can be many complications GVHD, infections
Collect new marrow, chemo to remove old immune system, infuse new marrow
Remission
Complete = disappearance of all measurable disease
partial = >50% reduction in disease
progressive disease is growth of >25% in new disease
Cure - >5 years without detectable disease
