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Platelets bud off of what part of megakaryocyte
Pseudopodia
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Growth factor required for platelet maturation
Thrombopoietin
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How long do platelets circulate in the blood?
7 days
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Do platelets have nuclei?
No
-
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Contents of dense granules
ADP, Ca2+
-
Granules contained in platelets (2)
-
Other name for Giant Platelet Syndrome
Bernard-Soulier syndrome
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What does platelet function analysis (PFA-100) measure?
Closure time (measures primary hematostasis)
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Low platelet count and value of low platelet count
- Thrombocytopenia
- <150 X 10^9
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High platelet count and value considered high platelet count
- Thrombocytosis
- >450 X 10^9
-
Elevated platelet count in context of pathological myelproliferation
Thrombocythemia
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Myeloproliferative disorders associated with thrombocythemia
- Essential thrombocythemia (>600)
- Polycythemia vera
- Myelofibrosis with myeloid metaplasia
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ITP
Immune thrombocytopenia purpura
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Autoimmune diseases associated with thombocytopenia (2)
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Conditions associated with intravascular overconsumption of platelets
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Condition associated with extravascular consumption of platelets
Hyperspleenism (platelets and blood pool in spleen)
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Congential bone marrow failure syndromes (leading to thrombocytopenia)
- Fanconi's anemia
- Schwachman-Diamond syndrome
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Condition associated with defect in DNA repair, leading to pancytopenia
Falconi's anemia
-
Bone marrow failure syndrome associated with pancreatic insufficiency
Schwachman-Diamond Syndrome
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CAMT
Congenital Amegakaryocytic Thrombocytopenia
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Conditions associated with genetic mutation of thrombopoietin receptor gene
Congential Amegakaryocytic Thrombocytopenia (CAMT)
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Condition associated with small platelets and thrombocytopenia
Wiskott-Aldrich syndrome
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Condition where there are antibodies to platelet receptors
Immune Thrombocytopenic Purpura
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Condition with microclots seen in small vessels where micro-clots are non-occlusive
- Microangiopathic Hemolytic Anemia (MAHA)
- RBCs get tangled in strands
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Conditions associated with intravascular consumption --> thrombocytopenia
-
Ig associated with ITP
IgG
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Platelet receptor attacked in ITP
IIb/IIIa
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Systemic microangiopathic hemolytic anemia (MAHA) resulting in ischemia of organs
Thrombotic thrombocytopenic purpura
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Enzyme lacking in congenital TTP
ADAMST13
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TTP diagnostic pentad
- Thrombocytonpenia
- MAHA
- Fever
- Neurological abnormalities (MAHA occurring in brain)
- Renal failure (MAHA occurring in kidneys)
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Enzyme that cleaves vWF
ADAMST13
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Consequence of deficiency of ADAMS13
- Large uncleaved vWF
- excessive adhesion --> clotting complications
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Condition with thrombocytopenia, MAHA, and acute renal failure
Hemolytic Uremic Syndrome (HUS)
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Hypercoagulable state resulting from idiosyncratic reaction to heparin
Heparin induced thrombocytopenia
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Ig associated with heparin-induced thrombocytopenia and the platelet antigen bound to heparin
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Deficiency in Bernard-Soulier syndrome
Glycoprotein Ib-IX (platelet can't adhere to subendothelium)
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Aggregation defect due to lack of binding with fibrinogen
Glanzmann's Thrombasthemia
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Function of glycoprotein IIb-IIIa in platelet aggregation
Cross-linking of fibrinogen
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Defect in Glanzmann's Thrombasthemia
Glycoprotein IIb-IIIa receptor
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Condition associated with α granule deficiency
Gray platelet syndrome
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Condition associated with dense granule deficiency
Wiskott-Aldrich syndrome
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TTP vs. HUS with respect to fibrogenemia
- TTP: hypofibrigenemia possible
- HUS: no hypofibrogenemia (localized to kidney)
-
Difference between aspirin and other NSAIDs with respect to platelet inhibition
- Aspirin: Irreversible
- Other NSAIDs: Reversible
-
Penicillin derivative that can cause dose-related platelet dysfunction
β-lactam
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Drugs besides aspirin that cause platelet dysfucntion
- pencillin derivatives
- Vaproic acid
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Drug that causes fight or flight response, leading to release of vWF and factor VIII
Desmopressin (DDAVP)
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Drug that enhances the clotting process by inhibiting fibrinolysis
Aminocaproic acid
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Tissue factor is associated with which coagulation pathway?
Extrinsic
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Factor VII is associated with which coagulation pathway?
Extrinsic
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Coagulation pathway that INITIATES the process of clot formation
Extrinsic
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Coagulation pathway that CONTINUES the process of clot formation
Intrinsic
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Factors (2) that contribute to prothrombin being cleaved into thrombin
-
Thrombin cleaves which factors?
-
Hemophilia A is deficiency in factor ___
VIII
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Hemophilia B is a deficiency in factor _____
IX
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Hemophilia C is a deficiency in factor ____
X
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Factors for which a deficiency would lead to both elevated PT and PTT
-
Treatment used on battlefield to stop heavy bleeding
Synthetic factor VII
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Normal PT and normal PTT
- PT: 12-15 sec
- PTT: 25-39 sec
-
Factor VIII cleaves what factor?
IX
-
What effect would vitamin K deficiency have on PT and PTT
Both increased
-
-
PTT
Partial thromboplastin time
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Time needed for coagulation pathway to yield end products
PTT
-
What does thrombin time measure?
Prothrombin conversion to thrombin and fibrinogen coversion to fibrin
-
If thrombin time elevated, what is the likely cause?
Abnormal fibrinogen
-
Effect of heparin on thrombin time, PT, PTT
- Thrombin: Increased
- PT: Can be increased
- PTT: increased
-
Effect of liver dysfuction on thrombin time, PT, PTT
- Thrombin time: Increased
- PT: normal
- PTT: increased
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Trade name of warfarin
Cumudin
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Effect of warfarin on PT
Increases
-
Effect of von Willebrand's disease on PTT
Usually elevated, but not always
-
What do you suspect if you have elevated PT, PTT and also thrombocytopenia?
Consumptive coagulatopathy (DIC, Kasabach-Merrit syndrom)
-
2 substances assoicated with regulation of fibrinolysis
- α2 antiplasmin
- Plasminogen activator inhibitor-1
-
What does protein C inhibit?
Va
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Mutation on active site of factor V where protein C can't bind and therefore can't apply breaks to clot formation
Factor V Leiden mutation
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What 2 products does antithrombin III inhibit
-
What will a deficiency in antithrombin III cause?
Thrombopilia
-
What compound does heparin enhance?
Anti-thrombin III
-
What would happen if anti-thrombin III deficient patient is given heparin?
Heparin would be useless
-
Enzyme that drives conversion of homocysteine into methionine
MTHFR
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Consquence of mutation MTHFR
Back-up of homocysteine--> blood vessels injured-->endothelial cells prothrombotic
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Antibody which causes lab anomaly which procudes elevated PTT
Lupus anticoagulant (antibody)
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Auto-immune syndrome that causes antibodies vs. phospholipids, possibly increasing risk of thrombus
Antiphospholipid syndrome
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Hyperhomocysteinemia and antiphospholipid syndrome associated with what kind of thrombi: arterial or venous?
Both
-
vWF is a carrier protein for what factor?
VIII (released when vWF binds subendothelium)
-
Treatment for von Willebrand's disease?
Desmospressin (DDAVP)
-
Differences in types of bleeding with von Willebrand's disease and hemophilia
- von Willebrand: superficial, mucocutaneous
- Hemophilia: deep tissues
-
PTT elevation difference in Hemophilia and von Willebrand
- von Willebrand: 2-3 seconds prolonged
- Hemophilia: severly prolonged
-
What does D-dimer measure?
- Measures end product of clotting
- Increased D-dimer can indicate thrombotic event
-
Syndrome where left iliac vein compressed by right iliac artery
- May-Thurner
- Prone to clot formation
-
Difference between heparin and tPA in clot treatment
- Heparin: prevents additional clot, but doesn't breakdown already existing clot
- tPA: breaks down existing clot, but doesn't prevent additional clots
-
-
Risk factors for arterial thrombotic events
- Hyper-homocysteinemia
- Lipoprotein A
- Anti-phospholipid antibody syndrome
-
Function of aminocaproic acid
Enhances platelet function
-
NATP
- Neonatal alloimmune thrompocytopenia
- Mother makes antibody vs fetal platelet antigen inherited from father
-
Possible causes of purpura fulminans (purpura + DIC)
- Deficiency in protein C or S
- Infection with gram neg bacteria (especially meningococcus)
-
Organized meshwork of thin-walled capillary venous sinuses with surrounding extracellular matrix
Bone marrow
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Differentiate between primary and secondary hemostasis
- Primary: platelet activation and aggregation--> plug
- Secondary: Coagulation cascade --> fibrin clot
-
Event that activates extrinsic cascade
Tissue factor exposed on inured endothelial cells
-
Factors in intrinsic pathway
-
Factors in extrinsic pathway
7
-
Factors in common pathway
-
Hemocrit value relative to hemoglobin value
Hemocrit should be 3x higher than hemoglobin
-
Measurement of the integrity of the extrinsic and final common pathways
Prothrombin time (PT)
-
Time (in seconds) for patient's blood to clot after addition of Ca2+ and activator of extrinsic pathway (thromboplastin)
PT
-
Activator of extrinsic pathway in PT test
Thromboplastin (tissue factor + phospholipids)
-
INR
- International normalized ratio
- Standardizes PT due to differences in thromboplastin sensitivities
-
Measures the integrity of the intrinsic and final common pathways
activated partial thromboplastin time (aPTT)
-
Contents of partial thromboplastin
Phospholipid only (no tissue factor)
-
Time for patient plasma to clot after addition of phospholipid and Ca2+
aPTT
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Coaguation confounding factors (3)
- High hematocrit (citrate anticoagulant concentration too high for plasma volume)
- Small blood sample size *citrate anticoagulant concentration too high for plasma volume)
- Sample opacity
-
Antiphospholipid antibodies can prolong ____, but are actually associated with _____
-
What is mixed in a mixing study?
- Blood sample that showed elevated PT or PTT mixed with normal plasma
- If factor deficiency, PT and PTT will return to normal
- If inhibitor, PT and PTT will still be abnormal
- (lupus anticoagulant is considered an inhibitor)
-
Vitamin K dependent factors
-
Factors made in the liver
- II (thrombin)
- 7
- 9
- 10
- 5
- ** all are vitamin K dependent except for 5
-
Condition where PT or INR prolonged and factor V depleted
Synthesis defect in liver
-
Target of warfarin
Vitamin-K dependent factors
-
Deficient factor in coagulation cascade with amyloidosis
- Factor X
- Protein fibrils will adhere to factor X
-
Deficient factor in coagulation cascade with myeloproliferative disease
Factov V
-
Deficient factors in von Willebrand syndrom (2)
- von Willebrand factor
- Factor VIII
-
Deficiencies in these factors cause NO bleeding risk (3)
- Factor XII
- Kininogen
- Prekallikrien
-
How is undfractionated heparin administered?
Continuous drip IV
-
How is low molecular weight heparin usd?
2x/day subcutaneous
-
How do you reverse unfractionated heparin?
Protamine
-
How is low molecular weight heparin administered?
Weight-based subcutaneous injection
-
How do you reverse low molecular weight heparin?
Can only partially reverse with protamine
-
What medication works as a vitamin K antagonist?
Warfarin (Comoudin)
-
How is warfarin administered?
Oral
-
How do you reverse warfarin?
Vitamin K and fresh frozen plasma (replaces factors that are lost)
-
-
When is oral vitamin K treatment vs. IV vitamin K treatment used
- If INR high and there is bleeding, give vitamin K in IV
- Otherwise, give oral vitamin K to replenish
-
Forms of heparin-induced thrombocytopenia
- Type 1: non-immune (clumping sequestration), can continue with heparin (no risk of thrombosis)
- Type 2: allergic reaction to heparin
-
How are platelets activated in type II heparin-induced thrombocytopenia?
Auto-antibodies link heparin and platelet factor 4 --> platelet activation --> thrombus formation
-
Types of Type II heparin-induced thrombocytopenia
- Early onset (exposed to heparin within 3 months --> formation of anti-heparin antibodies have formed)
- Delayed (days or weeks after stopping therapy)
-
When does delayed onset heparin induced thrombocytopenia manifest?
Days to weeks after discontinuation of heparin therapy
-
Risk of thrombus if you have heparin-induced thrombocytopenia type II
30-fold increase in risk (even if no thrombus forms, GIVE ANTICOAGULANTS - direct thrombin inhibitor usually used)
-
Methods for testing for heparin-induced thrombocytopenia
- 1. Serologic assay to test for circulating IgG, IgM, IgA heparin-dep antibodies
- 2. If serologic assay positive, do functional assay to detect heparin-dep antibodies that can react with Fx receptors on platelets
-
What happens if you give warfarin when the patient has active HIT-2?
- Warfarin-induced skin necrosis
- Venous gangrene in limbs
- (wait until platelets come back)
-
3 major mechanisms of DIC
- Excessive generation of thrombin from increased levels of tissue factor
- Impairment of normal anticoagulation (deficiencies in ATIII, protein S, protein C)
- Sustained release of PAI-1 -> suppression of fibrinolysis
-
Degredation product of plasmin-mediated proteolysis of cross-linked fibrin
D-dimer
-
Compounds which will prolong PTT in deficiency but are not associatd with bleeding risk
- Factor XII
- Kininogen
- Prekallikrein
-
Target of low molecular weight heparin
Xa
-
Action of direct thrombin inhibitor
Binding and inactivating thrombin without a cofactor (e.g. antithrombin)
-
Conditions that SHORTEN PTT
- Elevation of VIII
- Suboptimal sample collection
-
What kind of heparin in contraindicated for those with renal disease?
Low molecular weight heparin
-
Anticoagulant particular susceptible to drug-drug interaction
Warfarin
-
INR goals in VKA therapy for people with diagnosed AMI vs. people with high risk of AMI
- Diagnosed AMI: higher goal
- Increased risk: lower goal
-
DIC treatment
- Treat underlying condition
- Replace factors lost only if significant bleeding
- Anticoagulation only when coagulation is excessive
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