Card Set Information
Q1 Coagulation Heme Onc
Q1 Coagulation Heme/Onc
Platelets bud off of what part of megakaryocyte
Growth factor required for platelet maturation
How long do platelets circulate in the blood?
Do platelets have nuclei?
Contents of α granules
Contents of dense granules
Granules contained in platelets (2)
Other name for Giant Platelet Syndrome
What does platelet function analysis (PFA-100) measure?
Closure time (measures primary hematostasis)
Low platelet count and value of low platelet count
<150 X 10^9
High platelet count and value considered high platelet count
>450 X 10^9
Elevated platelet count in context of pathological myelproliferation
Myeloproliferative disorders associated with thrombocythemia
Essential thrombocythemia (>600)
Myelofibrosis with myeloid metaplasia
Immune thrombocytopenia purpura
Autoimmune diseases associated with thombocytopenia (2)
Conditions associated with intravascular overconsumption of platelets
Condition associated with extravascular consumption of platelets
Hyperspleenism (platelets and blood pool in spleen)
Congential bone marrow failure syndromes (leading to thrombocytopenia)
Condition associated with defect in DNA repair, leading to pancytopenia
Bone marrow failure syndrome associated with pancreatic insufficiency
Congenital Amegakaryocytic Thrombocytopenia
Conditions associated with genetic mutation of thrombopoietin receptor gene
Congential Amegakaryocytic Thrombocytopenia (CAMT)
Condition associated with small platelets and thrombocytopenia
Condition where there are antibodies to platelet receptors
Immune Thrombocytopenic Purpura
Condition with microclots seen in small vessels where micro-clots are non-occlusive
Microangiopathic Hemolytic Anemia (MAHA)
RBCs get tangled in strands
Conditions associated with intravascular consumption --> thrombocytopenia
Ig associated with ITP
Platelet receptor attacked in ITP
Systemic microangiopathic hemolytic anemia (MAHA) resulting in ischemia of organs
Thrombotic thrombocytopenic purpura
Enzyme lacking in congenital TTP
TTP diagnostic pentad
Neurological abnormalities (MAHA occurring in brain)
Renal failure (MAHA occurring in kidneys)
Enzyme that cleaves vWF
Consequence of deficiency of ADAMS13
Large uncleaved vWF
excessive adhesion --> clotting complications
Condition with thrombocytopenia, MAHA, and acute renal failure
Hemolytic Uremic Syndrome (HUS)
Hypercoagulable state resulting from idiosyncratic reaction to heparin
Heparin induced thrombocytopenia
Ig associated with heparin-induced thrombocytopenia and the platelet antigen bound to heparin
Platelet factor 4
Deficiency in Bernard-Soulier syndrome
Glycoprotein Ib-IX (platelet can't adhere to subendothelium)
Aggregation defect due to lack of binding with fibrinogen
Function of glycoprotein IIb-IIIa in platelet aggregation
Cross-linking of fibrinogen
Defect in Glanzmann's Thrombasthemia
Glycoprotein IIb-IIIa receptor
Condition associated with α granule deficiency
Gray platelet syndrome
Condition associated with dense granule deficiency
TTP vs. HUS with respect to fibrogenemia
: hypofibrigenemia possible
: no hypofibrogenemia (localized to kidney)
Difference between aspirin and other NSAIDs with respect to platelet inhibition
Penicillin derivative that can cause dose-related platelet dysfunction
Drugs besides aspirin that cause platelet dysfucntion
Drug that causes fight or flight response, leading to release of vWF and factor VIII
Drug that enhances the clotting process by inhibiting fibrinolysis
Tissue factor is associated with which coagulation pathway?
Factor VII is associated with which coagulation pathway?
Coagulation pathway that INITIATES the process of clot formation
Coagulation pathway that CONTINUES the process of clot formation
Factors (2) that contribute to prothrombin being cleaved into thrombin
Thrombin cleaves which factors?
Hemophilia A is deficiency in factor ___
Hemophilia B is a deficiency in factor _____
Hemophilia C is a deficiency in factor ____
Factors for which a deficiency would lead to both elevated PT and PTT
Thrombin (factor II)
Treatment used on battlefield to stop heavy bleeding
Synthetic factor VII
Normal PT and normal PTT
: 12-15 sec
: 25-39 sec
Factor VIII cleaves what factor?
What effect would vitamin K deficiency have on PT and PTT
Partial thromboplastin time
Time needed for coagulation pathway to yield end products
What does thrombin time measure?
Prothrombin conversion to thrombin and fibrinogen coversion to fibrin
If thrombin time elevated, what is the likely cause?
Effect of heparin on thrombin time, PT, PTT
: Can be increased
Effect of liver dysfuction on thrombin time, PT, PTT
Trade name of warfarin
Effect of warfarin on PT
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
Plasminogen activator inhibitor-1
What does protein C inhibit?
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
What 2 products does antithrombin III inhibit
What will a deficiency in antithrombin III cause?
What compound does heparin enhance?
What would happen if anti-thrombin III deficient patient is given heparin?
Heparin would be useless
Enzyme that drives conversion of homocysteine into methionine
Consquence of mutation MTHFR
Back-up of homocysteine--> blood vessels injured-->endothelial cells prothrombotic
Antibody which causes lab anomaly which procudes elevated PTT
Lupus anticoagulant (antibody)
Auto-immune syndrome that causes antibodies vs. phospholipids, possibly increasing risk of thrombus
Hyperhomocysteinemia and antiphospholipid syndrome associated with what kind of thrombi: arterial or venous?
vWF is a carrier protein for what factor?
VIII (released when vWF binds subendothelium)
Treatment for von Willebrand's disease?
Differences in types of bleeding with von Willebrand's disease and hemophilia
: superficial, mucocutaneous
: deep tissues
PTT elevation difference in Hemophilia and von Willebrand
: 2-3 seconds prolonged
: 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
Prone to clot formation
Difference between heparin and tPA in clot treatment
: prevents additional clot, but doesn't breakdown already existing clot
: breaks down existing clot, but doesn't prevent additional clots
Factors included in FFP
Risk factors for arterial thrombotic events
Anti-phospholipid antibody syndrome
Function of aminocaproic acid
Enhances platelet function
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
Differentiate between primary and secondary hemostasis
: platelet activation and aggregation--> plug
: Coagulation cascade --> fibrin clot
Event that activates extrinsic cascade
Tissue factor exposed on inured endothelial cells
Factors in intrinsic pathway
Factors in extrinsic pathway
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)
Activator of extrinsic pathway in PT test
Thromboplastin (tissue factor + phospholipids)
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+
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)
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
** 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
Protein fibrils will adhere to factor X
Deficient factor in coagulation cascade with myeloproliferative disease
Deficient factors in von Willebrand syndrom (2)
von Willebrand factor
Deficiencies in these factors cause NO bleeding risk (3)
How is undfractionated heparin administered?
Continuous drip IV
How is low molecular weight heparin usd?
How do you reverse unfractionated heparin?
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?
How is warfarin administered?
How do you reverse warfarin?
Vitamin K and fresh frozen plasma (replaces factors that are lost)
Vitamin K antagonist
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
: non-immune (clumping sequestration), can continue with heparin (no risk of thrombosis)
: 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
Compounds which will prolong PTT in deficiency but are not associatd with bleeding risk
Target of low molecular weight heparin
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
INR goals in VKA therapy for people with diagnosed AMI vs. people with high risk of AMI
: higher goal
: lower goal
Treat underlying condition
Replace factors lost only if significant bleeding
Anticoagulation only when coagulation is excessive