Heme 1 Cram Flashcards
EPO specifically stimulates ? cell to start erythropoiesis?
What are the steps of thrombopoiesis?
Prothromboblast- erythroblast
Liver puts C-TPO in circulation
C-TPO-> endothelium protein
Receptor forms on platelets, TPO enters cell, internalization
Activation, pseudopodia
Myeloid stem cells differentiate into ?
Lympoid stem cells differentiate into ?
Basophil
Eosinophil
Neutrophil
Monocytes
B cells- plasma cells
T cells
Natural Killer Cells
Define Hct
Define MCV
Define MCH
% of total blood that’s RBCs
Average size/volume of RBCs
Mean Cell Hgb- average quantitiy of Hgb in RBCs
Define MCHC
Define RDW
Define Anisocytosis
Average concentration of Hgb inside RBCs w/ size/vol accounted for
Red Cell Distribution Width, estimates range of volume/size of RBCs
Difference in sizes and volumes between RBCs
Most important function of RES?
What are the two types of RES?
Phagocytosis
Intravascular: RBC contents released into circulation, Hgb binds to haptoglobin, taken to liver
Extravascular: in spleen; Fe carried by transferrin to marrow; bili carried by albumin to liver
What part of the erythorcyte life cyle involves the extravascular RES?
What are the a/granular WBCs
WBC w/ Diff includes w/ cells
Fe bound to transferrin
Gran: BEN
Agran: LM
BLEMN Baso Lympho Eosino Mono Neutro
Neutrophil
Eosinophils
MC form of WBC w/ pale lilac granules
Forms bulk of pus
Bacteria infxn Inflammation Burn Stress
Red/orange granules
Allergic Parasitic AutoImm
Basophils
Lymphocytes
Blue/purple granules
Allergy Leukemia Hypothyroid
Agranular w/ sky blue rim around nucleus
Viral infxn Leukemia Mono
Monocytes
Cell mediated immunity release ? five cytokines
Agranular horse-shoe shaped nucles w/ gray cytoplasm, foamy
Viral/fungal infxn TB Leukemia Chronic Dz
IL Chemokine Lymphokine
IFN TNF
Define the following prefixes
A/An
Aniso
Pan
Poly
Poikilo
W/out
Unequal
All
Variable
Irregular
Define the following suffixes:
- cytopenia
- cytosis
- emia
- osis
- penia
Absent cells
Refers to cells
Refers to blood
Process or condition
Lack or deficient
What are the 3 severe Sxs of anemia?
What are some PE findings of anemia
Syncope Angina MI
Dyspnea Tachy- relates to severity Fatigue Geographic/smooth tongue Palpitations Pica Cheilosis- usually B12 deficient Spooning nails
? lab result is used to classify anemia?
If suspected anemia, and RTC is high, what are the causes of hemolysis?
MCV
Membrane abnormalities Enzymopathies Hgbopathies AutoImm Microangiopathic
DDx’s for microcytic anemia
When assessing for the cause, all lab results are compared to ?
Thalassemia Anemia Chronic Dz Iron deficient* Lead poisoning Sideroblastic
Fe Deficient
Microcytic anemia Dx chart
ITFTTSL Thal: UDU ACD: DDUDDNL IDA: DUDUDUH LP: UNU Side: UNU
What is the use of Ferritin
What lab result directly relates to the amount of Fe stored in the body
Storage protein w/in cells, reflects amount of stored Fe
Serum Ferritin
What is the use of Transferrin
What is the use of TIBC
What is the use of Hepcidin
Transport protein of Fe
Blood’s capacity to bind Fe w/ Transferrin
Hormone that regulates Fe storage, released by liver during infection/inflammation
What is the use of Erythroferrone
What is the use of Ferroportin
What is Hemosiderin
Suppresses hepcidin synthesis
Transports Fe from diet across intestinal lumen
Insoluble form of Fe only found inside of cells, formed when body has Fe excess
Where is Fe absorbed in the GI tract
How much does Fe fluctuate in/out per day
What is a normal Fe content for the whole body
Duodenal erythrocytes
1-2mg
3-4gm
How is Fe storage broken up across the body
What lab result can NOT be used to Dx Fe Deficiency
Under normal conditions, how much of transferrin is bound by Fe
RBC Hgb- 1800mg Liver parenchyma- 1000mg Spleen/ReticuloMacro- 600mg Marrow/Muscles- 300mg Plasma transferrin- 3mg
Serum Fe
1/3
What are the 4 stages of IDA development
How is mild/mod IDA Tx
How are severe cases Tx
1: dec ferritin (Fe stores)
2: RBCs turn hypochromic
3: Hgb dec
4: MCV dec
1st line w/ PO replacement:
Ferrous Sulfate 325mg QD, up to TID
IV Fe therapy w/ IMC consult
Ferrous Sulfate can interact w/ ? med
What is the most appropriate response to Tx of IDA
How long is Tx continued after values return to normal
Levothyroxin, take 4hrs apart
Hct returns halfway w/in 3wks, to baseline w/in 2mon
Hct/Hgb corrected w/in 8wks
6mon to replace stores
How is ACDz Tx
Define a thalassemia
Underlying condition
If severe- RBC transfusion or IV recombinant EPO
D/o of defected globin chain synthesis leading to reduced Hgb synthesis
What is the Hgb make up of Hgb F
What is the composition of Hgb Bart’s
What is the composition of Hgb H
What is the composition of Hydrops Fetalis
A2G2
GGGG
BBBB
–/– ‘0 alpha’
What Hgb is the last one to start developing in utero but lasts into adulthood?
How are thalassemia’s definitively Dx?
D
Electrophoresis
What type of Hx will PTs w/ thalassemia have?
What type abnormal RBC morphologies may be seen on smears?
FamHx
Hx of microcytic anemia
Microcytes
Acanthocytes- Greek, thorn
Codocytes- target cells
What would Chromosome 16 look like in a PT w/ A-Thalassemia (minima/trait)
What would the chromosome look like in a PT w/ A-Thalassemia minor
AA/AA Normal
AA/A- Trait
AA/– Homozygous
A-/A- Heterozygous
What would Chromosome 16 look like in a PT w/ A-thalassemia Intermedia
What form of A-Thalassemia mainly affects Asians or Blacks?
Hgb H: A-/–
Heterozygous A-/A- Asian
Homozygous AA/– Black
What is the life expectancy for PTs w/ A-thalassemia minor trait
How are PTs w/ Hgb H Dz managed
Normal
Daily folate, avoid iron
Transfusion during hemolytic exacerbations
What drug classes do PTs w/ Hgb H Dz need to avoid
Since B-thalassemias have impaired B production, what substitutions can occur?
Anti malaria bacteria
Sulfa
Analgesis
TB
Excess A chains can pair w/ D chains (HbA2) or G chains (HbF)
What happens to the A-globins in cases of B-thalassemia
What PTs have more severe cases of B-thalassemias?
Unstable and damage RBC membranes
Homozygous impaired B-globin synthesis
What two types of B-Thalassemia have basophilic stippling
What form of B-Thalassemia has nucleated RBCs?
B minor/trait
B intermedia
Major- Cooley’s Anemia
What form of thalassemia appears abnormal on electrophoresis
Only ? thalassemia has heterozygous genes?
B, due to G/D globin chains
G= Hgb F
D= Hgb A2
B-Thalassemia minor
B thalassemia intermedia globin combos
B thalassemia major globin combos
B+/B+
Bo/Bo or,
B+/B+
? Thalassemia is transfusion dependent and is a majority of HgF
How is A-Thalassemia trait or mild B-thalassemia Tx
B-Thalassemia Majors
None, identify to avoid future eval/Tx for Fe deficiency
Hgb H- Folic acid supplements and avoid Fe/Oxidative drugs
How is B-Thalassemia intermedia/major Tx
What can develop if these PTs are over Tx?
Transfusions Folate Splenectomy
Marrow Transplant- TxOC for Major
Too many transfusions= iatrogenic Fe overload syndrome
What lab result is Dx of Sideroblastic anemia
What causes this d/o
Bone marrow Fe >10% ringed sideroblasts
Serum Fe is avail but isn’t utilized by mitochondria= RBCs w/ iron granule in mitochondria
What lab method is used to visualize ringed sideroblasts
Why are stippled basophils also seen in this lab test?
Prussian blue (Perl’s reaction) shows ring of blue granules
Indicative of disrupted erythropioesis
How is sideroblastic anemia Tx
How does lead poisoning cause anemia
Support Hgb <7= PRBC transfusion PO Pyridoxine (B6)
Impairs heme synthesis
Inc RBC destruction
What lab result is used to differentiate lead poisoning as a recent or chronic exposure
How is lead poisoning anemia Tx
Free Erythrocyte Protoporphyrin
Inc L, Normal FEP= recent
Inc L, Inc FEP= chronic
1st: Succimer
2nd: Penicillamine
Severe/lead encephalopathy: Dimercaprol + EDTA (crosses BBB- causes Peds neuro/learning disabilities)
What are the 4 conditions that present w/ basophilic stippling?
What do the lead panel results look like for results w/ stippling in them?
B minor/intermediate
Lead poisoning
Sideroblast
Inc TIBC Fe
Low Ferritin
What are the two types of Macrocytic anemias due to?
Mega:
B12/Folate deficient, Drugs
Non-mega: AHEAD MS Alcohol Hypothyroid Emphysema Accelerated erythopoiesis Drug induced Marrow d/o Surface area, inc on RBC
To initiate hematopoiesis, EPO stimulates ? cell
Megaloblastic anemia has their etiology starting w/ ? cell
Proerythroblasts
Erythroblastic stage
If hypersegmented neutrophils are seen on a peripheral smear, this indicates?
What is the criteria for hypersegmented neutrophil?
Megaloblasts in marrow
Neutrophil nuclei w/ +6 lobes or,
+3% neutrophils w/ five nuclear lobes
How is it brought into the GI system for use
HCl releases pepsin, seperates B12 from foods
Parietal cells release IF, absorbs B12 in terminal ileum
TC2 from WBCs carries B12
Liver contains ?mcg of stored B12 meaning it takes ? long for a deficiency to occur
What is B12 roles in DNA synthesis
A lack of B12 causes a build up of ?
2-5000mcg
>3yrs after absorption ceases
Used for converting m-CoA into s-CoA in mitochondria
Methylmalonic acid
What is the most sensitive test for B12 deficiency at the cellular level
The lack of B12 for DNA synthesis causes ? to be formed
MMA test
Hypersegmented neutrophils
What types of diets can cause B12 deficient anemia
? type of drug abuse can cause this?
What is the name of the cobalamin metabolism d/o that can lead to this?
Strict vegan no dairy, meat, fish
Only breast fed baby of vegan mother
NO- present w/ spinal degeneration
Imerslund Grasbeck Syndrome
What are the biggest 3 Sxs that present w/ B12 anemia in order of presentation
Why does B12 deficiency cause neuro Sxs?
Peripheral neuropathy: paresthesia of hands
Ataxia
Dementia
Involved w/ myelin production
What is the ‘5 P’s of B12 Deficiency” mnemonic?
Pancytopenia Peripheral neuropathy Papillary atrophy (atrophic glossitis) Posterior column neuropathy Pyramidal tract signs
What is the only lab result that differs between B12 deficiency anemia and pernicious anemia?
How is B12 deficiency anemia Tx
IFBA/Serum Gastrin tests
Genetic cause: lifetime Tx
Reversible: until corrected and Sxs are gone
Vit B12 but NOT nasal route
Pts w/ B12 Deficiency anemia but no Sxs are Tx w/ ?
What PT population may need more aggressive repltion and how is that done?
PO 1000mcg/day
IM 1000mcg/mon
Sx anemia Neuro/psych Sxs Pregnant 1000mcg every other day x 2wks Cyanocobalamin qMon or, Hydroxocobalamin once q2-3mon
How is Pernicious Anemia Tx
How are PTs w/ Lichtheims Dz that have B12 and folate deficiency Tx
Parentera Tx for life
Initial dose 1000mcg IM or DeepSQ x 4wks then
1000mcg qMon
Replace B12 first, prevents neuro Sxs
Folate would only correct Heme Sxs, not neuro
What is the sequence of response to Tx for B12 deficiency
Where is folate acid normally found, absorbed and how can it be destroyed?
Erythropoiesis normalizes 2-3 days
Hypersegment neutrophils gone by 14 days
Neuro Sxs gone in 6mon if reversible
Fruit Veggies Animal protein
Prolonged cooking
Prox small intestine
Body normally stores about ? folate which is a ? supply
What meds were highlighted as causing folate deficient anemia
5000mcg
2-3mon
Anti convulsants
ABX- sulfas
HIV meds
How is folate deficient anemia Tx
PO 1000mcg PO per day x 1-4mon or until complete hematological recovery
What would be the difference in lab results form someone w/ folate deficient anemia and someone w/ combo B12 and folate anemia
What are the two classic characteristics of megaloblastic anemia not seen in Non-Magalo Macro Anemia
Combo: Dec B12, Inc MMA
Oval macrocytes
Inc RDW
When is a marrow biopsy warranted during a non-megalo work up?
Sine there are no megalobasts in non-mega anemia, what would be seen on a marrow sample?
No Aplastic CLDz ETOH
Unexplained megalo or,
Myelodysplasia suspected
Megaloblastoid RBC precursors (proerythroblasts) w/ nuclear chromatin
? anemia has inc RBC surface area
? meds can cause this type of anemia w/ inc surface area
Non megalo macro- inc deposition for cholesterol/lipids
Benzenes
Define MDS
What are 3 causes
Marrow d/o of ineffective erythropoiesis, mutated menatopoietic stem cell
Chemo/Rad Tx
Benzene meds
PTs w/ MDS are at risk of developing ? type of leukemia
How is this Dx fore shadowed?
AML
Pre-leukemia syndrome, precedes Dx by 10yrs
How do PTs w/ MDS present in clinic?
What lab report is Dx
Fatigue out of proportion to anemia
Dec Hct
Inc B12 and RDW
All other values Norm
What is the difference in lab results between Non-megalo anemia and MDS
What is the best recognized morphologic abnormality of erythrocytes in MDS
What lab tests are key to the Dx of MDS
What are 3 Dzs that can present mimicking MDS but must be r/o
MDS- inc RDW
Oval macrocytosis
Peripheral smear
Unilateral marrow biopsy
HIV
B12/Folatedeficient
How is MDS Tx
Support/Sxs Transfusion Hgb <7 Platelet transfusion if <50K before surgery <20K and bleeding <10K and ASx Chemo/Marrow transplant
Can you use MCV for Dx B12 deficiency?
What are the 4 causes of normocytic anemia
No, lacks sensitivity/specificity for cobalamin deficiency
Chronic Dz
Aplastic/Hemolytic anemia
Acute blood loss
What are the 3 causes of hemolytic anemia
What is the 2nd MC anemia
Hereditary Spherocytosis
G6PD
Sickle Cell
Normocytic Anemia, ACD
What is the pathophysiological reason behind normocytic anemia, ACD?
Inflammation causes:
Disturbed homeostasis- dec Fe and RBC
Macrophages release IL-6, stims hepatocytes, release hepcidin= dec Fe absoprtion/release from macrophages
Inflammation dec avail Fe for erythropioesis
When marrow erythropoiesis fails, what organ picks up 25% of the extramedullary work load?
How is Normocytic ACD Tx
Liver
Fe supplements (unless no deficiency) Transfusions ESA w/ anemia Sxs AND Hgb <10g: CA on chemo CKD GFR <30 HIV Tx w/ myelosuppression
What is the goal of Tx for Normocytic ACD
What lab result is not used for routine measurement
Hgb 11 and Hct >33%
Serum EPO
Define Aplastic Anemia
What are the two types of Aplastic?
Hypoproliferative anemia due to marrow failure, leading to pancytopenia
Primary: IgG against marrow
Secondary: acquired
What is the #1 cause of aplastic anemia
What metals can cause it?
What toxins can cause it?
What viruses can cause it?
Idiopathic
Gold Arsenic
Glue Benzene Solvents
Seronegative non A-G hepatitis
HIV
Other HSV
EBV
What is the typical bimodal presentation of Aplastic Anemia
What are the Sxs
What are the Signs
15-25 and >60y/o
Thrombocytopenia
Anemia
Neutropenia
Pallor Purpura Petechiae
What PE findings are absent in aplastic anemias?
What lab result is the hallmark of aplastic?
How is a Dx confirmed?
Hepatosplenomegaly
Lymphadenopathy
Bone tenderness
Inc fat, dec stem cells= Pancyotpenia
Hypocellular bone marrow
What does the term ‘non-clonal’ mean?
What are two non-clonal d/os causing aplastic anemia?
Not bone marrow
Hypersplenism
Lupus
How is aplastic Tx
What are the intrinsic etiology of hemolytic anemia
Young PT w/ functional status= marrow transplant
Older PT- ImmSupp to let remaining marrow recover
Defected RBC, hereditary
Membrane defect- spherocyt.
Oxidaiton- G6PD
Hgbopathies- Sickle, Thalassemia
What are the extrinsic factors causing hemolytic anemia
External factors
Immune: AutoImm, drugs
Microangiopathic- TTP HUS Cardiac valve hemolysis
Infection- Borrelia Malaria Clostridium
What are the two types of schistocytes seen in hemolytic anemia
What will lab analysis show?
Bite cell
Helmet cell
Dec haptoglobin Inc: Indirect bili Hemoglobinuria LDH RTC
What is the MC intrinsic hemolytic anemia
What does this issue become evident
Hereditary spherocytosis- abnormal spectrin/actin (RBC membrane structure)
Less deformable and can’t pass through spleen= rupture and trapped
What type of hereditary passage does hereditary spherocytosis have?
What lab results are indicative of a Dx
Auto Dom- abnormal gene from one parent= Dz
Inc MCHC
Neg Coombs test= not AutoImm
Inc osmotic fragility test
How is hereditary spherocytosis Tx
What is the MC enzymatic d/o of RBCs
Support/Transfuse Hgb <7
Folic supplements
Splenectomy- rarely needed
G6PD- RBCs hemolysis when under oxidative stress
What type of hereditary passage does Sickle have?
What PT population does it affect most?
X linked recessive
SE Asia
Mediterranean- severe, chronic hemolytic anemia
AfAM
Define Homo/Hetero/Hemizygous
When radicals are formed during oxidative stress they attack ?
Homo: two identical alleles
Hetero: two different alleles
Hemi: only one allele
DNA Lipids Proteins
Define Favism
What type of cell is Dx of G6PD
All PTs w/ favism= G6PD
Not all G6PD= favism
Heinz bodies- seen w/ crystal violet stains
Causes bite cells during spleen passage
What 2 blood d/os have bite cells?
What will lab analysis of G6PD show
Normo, hemolytic anemia
Normo, G6PD
Dec: haptoglobin G6PD enzyme
Inc: Indirect bili LDH RTC
When are splenectomys recommended for G6PD PTs
What genetic d/o causes sickle cell?
Severe episodic/chronic hemolysis
Auto Recessive- point mutation on 6th AA of B-globin gene
HbA, HbS= trait
HbS, HbS= Dz
How/why is Sickle Cell Dx so early
The sickling of RBCs is sensitive to ?
Hgb F drops off= Hgb S
Intracorpuscular concentration of deoxygenated hgb
When is sickling of RBCs increased?
What are PTs w/ Sickle Trait at risk for?
Dehydration
Changes to oxygen dissociation curve: hypoxia acidosis altitude
Sudden cardiac death
Rhabdo
What is a visible to the eye Sx of a chronic sickle cell anemia PT
What are the MC sites for sickle PTs to have vaso occlusive crisis?
Ulceration on lower anterior tibia
Spine
Kidneys
Long bones
Lungs
Define a sickle Acute Chest Syndrome
If Sickle PT has osteomyelitis, ? is the microbe
Angina
Hypoxemia
Pulm infiltrates on CXR
Salmonellae
What will be seen on lab analysis of Sickle?
What is the hallmark of hyosplenism in sickle cell
Inc WBC, indirect bili
Dec Hct
Howell Jolly bodies
Target cells
How are sickle cell PTs managed for Tx
When do these PTs need transfusions?
FOAHL Folic acid- 1mg PO per day Omega 3- reduce occlusive ACEI if + microalbuminuria Hydroxyurea and L-glutamine for pain crisis
Stroke
Occlusive/pain crisis
Acute chest syndrome
Priapism
When are Sickle PTs admitted
How can this Dz be definitively Tx
Acute chest syndrome
Aplastic crisis
Unresponsive Pain crisis
Stem cell transplant before end organ damage
How/why does acute blood loss lead to anemia
Baroreceptors release vasopressin
Shifts fluids extra to intra cellular= hemodilution
Hypovolemia changes to anemia
Marrow response takes 7 days to respond w/ inc RTC
Define Massive Transfusion
Doing these procedures can cause ? metabolic shifts/issues
> 50% of PTs volume in 24hrs
10 PBRC units in 24hrs
Metabolic acidosis Hypo Ca/thermia HyperK Coagulopathy Dilutional thrombocytopenia
What is the MC transfusion reaction
How can the chances of this reaction be reduced
How is it Tx
Leukoagglutinin- reaction to Abs on WBCs from PRBCs; febrile non-hemolytic reaction
F/c w/in 12hrs of receipt
Leukopore filters- filters donor WBCs out prior to storage
Diphenhydramine
Acetaminophen
CCS
What causes acute hemolytic transfusion reactions
What is the MC cause of this reaction
When do the most severe reactions occur
Mismatched ABO/Rh blood= massive intravascular hemolysis
Clinical error
Surgery under general anesthesia
What are the classic S/Sxs of AHTR
PTs under anesthesia can’t/wont present with classic signs of AHTR but will present w/ ?
Fever/rigor HOTN HA/back pain
Oliguria Bleeding
How long for DHTR to present w/ ? unique Ab is seen in this type of reaction
What is the name of the reaction
5-10 days
Alloantibody- produced against foreign tissues
Anamnestic responses- enhanced immune response
Blood product contamination is usually by ? type of microbe infecting ? blood cell
How would PTs present if the not MC microbes infected their product
What is the most and least likely transfusion associated infection?
Gram neg- platelets not refrigerated
Gram Pos=
Fever, Bacteremia
Rarely sepsis
Most: Hep B
Least: HTLV
How does kidney damage occur from blood product contamination?
Fresh Whole Blood
Gram neg microbes causes transfusion endotoxins
RBCs Plasma WBCs and Platelets
Kept for <24hrs
Use: cardiac surgery/massive hemorrhage, +10 units in 24hrs
Exact blood match- MUST
PRBC
Define CMV negative, leukocyte reduced filtered RBC
MC transfused product
1 unit inc Hgb x 1g and Hct x 4%
1 unit= 300ml vol inc
Dec leukocyte blood to prevent transmission of CMV, causes post-transplant I/G/H Dz
When are CMV neg, WBC reduced RBCs used
How long can frozen RBCs be stored?
Hx febrile non-hemolytic transfusion reactions
Cardiovascular surgery
Transplant candidates
Chronically transfused PTs
10yrs- expensive, reserved for rare blood types
Define Irradiated RBCs
What part of blood contains coagulation factors
Completely removes WBCs
Used for ImmComp PTs
Plasma
When is FFP used
1 unit of apheresis platelets= + units of whole blood platelets
PTs w/ active bleeding or at high risk for bleeds
6 units
1 unit= inc platelets by 5-10K w/in 1hr
Define Platelet refractoriness
Platelets don’t inc w/in 1hrs after transfusion
Non-Imm MC cause: sepsis
Imm: Abs against HLA Ags are primary cause
What is the use of Freeze Dried Plasma
Who is universal donor and recipient
Only avail for SF, sterile water reconstitute
D: O-
R: AB+
Erythroblastosis Fetalis
How is it prevented
Immune Hydrops or Rh Dz of Pregnancy
Mother Imm system destroys Rh+ cells in baby
ImmGlob 300mcg @ 28wks W/in 72hrs of terminated pregnancy Post-any vaginal bleed Amniocentesis or chorionic villi sample Avoid manual removal of placenta
What are the 3 steps of forming the initial platelet plug
This process requires ? two phases to work togeth
Adherence
Activation
Aggregation
Vascular
Platelet
Define Secondary Hemostasis
What are the 3 phases
Cascade of activating clotting factors to form fibrin clot
Vascular
Platelet
Coagulation cascade phase
What happens during vascular phase of hemostasis
What happens during platelet phase of hemostasis
What happens during coagulation phase?
Spasms of smooth muscle, lasts 30min
Endothelial cells release vWFs, results in platelet adhesion
Enzyme thrombin activates fibrinogen to form fibrin= clot
Define vWF
This cell carries ? clotting factor
Blood glycoprotein used as bridge for platelet aggregation
Factor 8
Steps of platelet adhesion
Adhere to endothelial cells
Activated platelets release ADP and thromboxane
ADP binds to platelet receptor, activates Gp2b/3a to accept fibrinogen
Platelet aggregation= plug
? binds fibrinogen and is considered the final common location for platelet to platelet aggregation
What activates the intrinsic pathway
This in turn activates ?
Gp1b/3a
Trauma exposing blood to subendothelail collagen
Extravascular/tissue trauma phase
What is the only clotting factor used in all of the pathways?
There is no Factor _
Factor 4: Ca ions, accelerate clotting pathway
6- prothrombinase, combo of 5 and 10 factors
Coagulation Cascade
Xa + Va= prothrombinase 2 to Thrombin Thrombin to 1 Fibrin + stabilizer Cross linked fibrin- Factor 8 Clot
What do blood banks add to Ca2 during clot formation
Thrombin is needed to activate ? factors
Citric acid
8 11 5 13
Fibrin stabilizer is factor ?
What is it’s function
13
Combos w/ thrombin and Ca= Factor 13a- caused cross link fibrin
What clotting factors are vital to the common pathway?
Factors _ + _= Activated 10,a
1 2 4 5 10 13
8a + 9a
Thrombokinase
Where is the intrinsic pathway found?
What is the most important part of the extrinsic pathway?
In vasculature system
Tissue factor
TF + 7a= 10a
What lab test is used to identify issues in the intrinsic, extrinsic pathway
What are the Vit K dependent factors
In: PTT
Ex: PT
2 7 9 10
Protein C, S
Vit K deficiency= ?
Coumadin is a ?
Prolonged PT, extrinsic
Vit K antagonist
Inhibs 2 7 9 10 Protein C, S
Why is coumadin bridged w/ heparin?
Factor 1
Coumadin causes transient hypercoagulable state during Protein C decreases faster than coagulation factors
Fibrinogen- activated to form fibrin
Define DIC
What carries Factor 8
Depleted fibrinogen and fibrin (1A) levels
vWF
A deficiency of vWF can lead to ?
What factors are involved w/ Hem A, B and C
Defected platelets and coagulation= Von Willebrand Dz
Hem A: Factor 8
Hem B: Factor 9
Hem C: Factor 11
Platelet problems usually present as ?
What is LESS severe, platelet of coagulation d/o
Mucous membrane bleeds
Platelet
Platelet count below ?K puts PTs at risk for spontaneous massive hemorrhages
Coagulation d/os are usually associated w/
<10K
Large vessel bleeds- Hemarthrosis Hemotoma Ecchymosis Excessive bleeds
What is the hallmark red flag to bleeding
Define Menometrorrhagia
Hemarthrosis causing pain
Irregular prolonged and heavy bleeds
What are 4 types of life threatening hematomas
How are issues w/ intrinsic pathway tested for?
Air way compression
Compartment syndrome
Retroperitoneal
CNS bleeds
PTT
Stims of Factor 12
Detects issues of 1 2 5 8 9 10 11 12 and Fibrinogen
Normal PTT= ?
PTT >100sec = ?
Normal aPTT is ?
60-70sec
Spontaneous bleeds
25-40sec
How is the extrinsic pathway tested?
What does the INR test
Thromboplastin to plasma, wait for fibrin formation
Detects issues of 2 5 7 12 and fibrinogen
Norm= 10-14sec
Extrinsic path based on PT
0.8-1.2
What is the target INR for PTs w/ DVTs, PEs, AFib or valve HDz?
What is the target range for PTs w/ mechanical valves or recurrent MIs?
2-3
2.5-3.5
Hemophilia ? is only in males due to it being passed by ?
Hemophilia ? is in either gender equally
A and B, X-linked
C
How do cases of hemophilia present
What will lab results show
What are the 3 classifications
hemarthrosis/Arthropathy
OOP bleeding during surgery
aPTT prolonged
Factor activity of-
Severe: <1%
Mod: 1-5%
Mild: >5%
Severe hemophilia classification
2-4 times/mon Factor activity <1% Spontaneous hemorrhage from infancy Frequent hemarthrosis/muscle bleeds Dx by 2y/o
Moderate hemophilia classification
4-6x/year Factor activity 1-5% Hemorrhage due to trauma/surgery Occacsional spot hemarthrosis Dx by 5-6y/o
Mild hemophilia classification
Uncommon bleeds Factor activity >5% Bleeds due to trauma/surgery Occasion spot hemorrhage Dx later in life
How is hemophilia Tx
What Tx method is avoided in PTs w/ factor concentrations starting in childhood
Replace clotting factors
DDAVP for mild Hem A
Hemophilic arthropathy
What are the 3 types of VWDz
1: partial quant of vWF
2: qual of vWF
A absence
B binds w/ GP1b
M dec platelet dependent function (weak bonds)
N doesn’t carry Factor 8
3: complete quant deficient vWF
How is VWDz Tx
Circulating antigoagulants usually neutralize ? clotting factors
When is the Dx considered
DDAVP for Type 1, 2a, 2b
Recombinant vWF for Type 2 and 3
No FFP (no/low vWF)
2 5 8 9
PTs w/ inc PTT or PT that doesn’t correct w/ repeated mixing test
Pts w/ circulating anticoagulatns and Hemophilia are Tx w/ ?
If PT doesn’t have hemophilia they’re Tx w/ ?
Recombinant Factor 7
Cycophosphamide
CCS
Rituximab
During coagulopathy of Liver Dz Tx, all factors are dec except?
If this factor is dec, ? dx is considered
8
DIC
As the severity of a liver Dz inc, what lab value also inc?
What is the primary lesion in DIC
PTT
Mild: Inc PT, N PTT
Severe: Inc PT and PTT
Excess tissue factor causes overwhelming formation of thrombin/fibrin
What are the two phases of DIC
What types of cells are seen in DIC?
Ischemia to Hemorrhagic
Schistocytes
What is the natural blood thinner of the body that will be dec in disseminated DIC
A DIC score of _ or more is indicative of higher mortality
Anti thrombin 3
5 or higher
How is Disseminated DIC Tx
When is anticoagulation therapy recommended?
If precipitated by sepsis- Activated Protein C (regulated activity of thrombin)
Hemostatic therapy- platelets and FPP
Arterial thromboemboli w/ mural thrombus
Migratory thrombophlebitis w/ Trousseau syndrome ( 2nd leading cause of death in CA PTs)
What is the sequence of platelet development
What are the granules inside of platelets
Myeloid Progenitor Megakaryoblasts Megakaryocytes Platelets in plasma membrane
ADP, Thromboxane A2
If attempting to r/o pseudothrombocytopenia, what color tube is used for the draw?
This pseudo condition is AKA ?
Platelet d/os of ? etiology are more likely to be overlooked
EDTA tube- sodium citrate (light blue)
Platelet clumping
Quant:
VWDz
Acquired d/o
Congenital
What is the MC cause of immune thrombocytopenia
What are secondary causes of Immune Thrombocytopenia
What is the time difference between chronic and acute
ITP
AutoImm
HIV/HCV
Drugs
Acute <6mon (kids, 2-10yr)
Chronic >6mon (adults w/ HIV AutoImm APS or Hep B/C
How does ITP present
What PE finding is considered uncommon
Mucosal bleeds
Splenomegaly
What is the sequence of bleeding in ITP as platelet numbers fall?
What does the absence of cutaneous petechia mean in this condition?
Skin- petichae/purpura
Mucous membranes
Viscera
Low chance of inracranial hemorrhage and there for, less severe case of ITP
What criteria are used for drug induced ITP Dx
How is it Dx
What are the 4 scenarios to do this Dx step
Severe thrombocytopenia
Mucotaneous bleeds x 7-14 day
after start of new drugs
Marrow biopsy
> 50y/o to exclude MDS
Unexplained cytopenia
Therapy failure
Prior to splenectomy fo Dx confirmation
What is the mainstay of ITP Tx
How is relapsed/persistent ITP Tx
How is relapsed/worsening ITP Tx
REduce bleeds w/
CCS +/- IVIG or anti-D
If severe hemorrhage present- platelet transfusion
Monoclonals Rituximab or
Anti-D or
IVIG or
TPO
Splenectomy
When is serial platelet counts used for monitoring ITP Tx
PTs w/ acquired HIT are at risk for ?
ASx and Platelets above 30K
Art and Ven thrombosis for wk/mon after heparin d/c
How does HIT develop
How is a Dx confirmed
When is Tx started
IgG against Platelet Factor 4
PF4 Ab enzyme linked ELISA
+= confirm w/ SRA
Immediately when Dx is SUSPECTED
When is a HIT Dx suspected
5-14d post heparin exposure
50% decline from baseline
Necrotic skin at site
Thrombosis
4Ts w/ 8pts max:
Low: 3 or less
Int: 4-5
High: 6 or more
How is this condition scored?
2pts for
Platelets dec x 50% and 20K or higher
Clear onset between days 5 and 10 or,
Platelets fall under one day
New thrombosis/necrosis or systemic reaction
How is HIT Tx
Direct thrombin inhib- Argatroban Bivalirudin Fondaprinux until +100K
Warfarin c/i until platelets at 100K
INR goal 2-3
Duplex doppler LE to r/o DVT
How long is anticoagulation Tx post-HIT maintained
What refereal is placed for these PTs
Thrombosis= 3-6mon after platelet recovery
No thrombosis= 30 days after platelet recovery
ALL PTs w/ HIT see a hematologist
Define TMA
This condition includes ?
What findings are indicative of TMA Dx
Vascular injury leading to thrombi in microvasculature
TTP HUS
MAHA- schistocytes
Thrombocytopenia
Define TTP in a TMA case
What is the pentad of TMA
What part is most associated w/ TTP
AutoAbs against vWF cleave protease ADAMTS-13
Fever Anemia Thrombocytopenia Renal Dz *Neuro complications
Renal Dz in TMA is most associated w/ ?
How is this condition defined
HUS
TMA is a main cause of CKI in ? PTs
These PTs all present w/ ? Triad
Kids
Petechia HTN RF
What typically precedes TMA HUS
? stool culture results may be seen here?
GE w/ E Coli O157 STEC
+ Ecoli 157
Shiga toxin
What is the difference in lab results between acquired TTP and inherited
What is needed for a Dx of complement mediated HUS
Ac: dec ADAMTS12
In: absent
Mutated genes that encode complement
How is TMA Tx
What is the exception
Immediate plasma exchange as soon as Dx is made
Platelet transfusion c/i
2nd line: if refractory; CCS Rituximab IVIG Cyclo Splenectomy
CKI= dialysis
Shiga/Ecoli origin= support Tx only
? med can cause qual platelet d/os
Thalassemia Dx is only considered after ?
ASA
Exclusion of IDA
PT w/ DM or GERD may develop ? type of anemia?
4 ABX that can induce oxidative stress
B12 deficient macro
Sulfonamide
Nitrofuranotoin
Quinolone
Dapsone
Deterioration of ? Dz will worsen normocytic anemia
What miscellaneous things can cause aplastic anemia
CKDz
Paroxysmal nocturnal Hbguria
Preg Anorexia Thymoma
3 times nucleated cells are seen?
Define Thrombus
Define Embolus
Define Embolism
WBCs
Cooleys, Sickle
Blood clot
Fragment of thrombus traveling
Lodged embolus
Define Coach Class Syndrome
What are the ‘strong’ RFs for VTEs
Classic VTE Hx: travel surgery/trauma CaHx
Spinal cord injury Hip/leg Fx Hip/knee replacement GenSurg Major trauma
? lab result has strong evidence against a VTE
What is the initial image of choice for VTEs
What test is used if CT is unavail
D-dimer <500ng via Rapid Quant ELISA
CT-PA
VQ scan
What is the ToC for detecting proximal DVTs
What is an invasive Dx test that can be done
VUS
Pulm Angiography
How are VTEs Tx
What is the safest anti-coag Tx for PTs w/ GFR <30
How is LMWH or Heparin reversed
LMWH- Enoxaparin
UFH
Warfarin
Protamine Sulfate
Coumadin is c/i in ? PTs
Heparin affects ? factors
Warfarin affects ? factors
Dabigatran affects ? factors
Factoa Xa inhibitors -ban affect ? factors
Pregnant
2a 7a 9a 10a 11a
2 7 9 10
2a
10a
Why are Factor Xa inhibitors used for VTE Tx
What are the risks
No Lovenox bridge needed
ARE-ban
No monitoring or daily injection
Irreversible binding
Can’t monitor PT compliance
How long are VTE PTs on anticoag therapy
How long are PTs that have idiopathic VTE or have low/mod risks of bleeds on therapy
What regime are Ca PTs placed on
1st one: 3mon
No stop date
D-dimer repeat in 1mon
Extended w/ LMWH
What PE measurement indicates DVT
What are the MC S/Sx of PE
Calf diameter >3 measured at 10cm below anterior tibial tuberosity
Sinus Tachy
Non-specific ST/T changes
S1Q3T3
Well’s Score
S/Sx
PE likely
Tachy
Imm/Surg
Prior DVT
Hemptysis
CA current/Tx 6mon
>6 high <2 low
When is a D-dimer taken w/ a Wells score
<4
Dimer<500= neg
>4
CTPA, no D-Dimer
CHA2DS2VASc score
Annual risk for TIA/CVA
2 or more= anticoag
CHF HTN Age >75 DM Stroke TIE TE Vascular Dz Age 65-74 Sex, female
Max 9
<74, max 8
