Defects in Hemostasis Flashcards
1
Q
VWD (types and dx)
A
- COMMON; 1-3% US pop (often unnoticed in women w/ family hx immense menses)
- VWF is coded on chromosome 12
TYPES
- 1 - low VWF so mild and late dx; responds to desmopressin (auto dom)
- 2- abnormal VWF; moderate and earlier dx; tx w/ VWF concentrate (auto dom)
- 2A - loss of high wt VWF monomers
- 2B - excessive platelet binding to VWF (thrombocytopenia); so only one w/ inc RCoF
- 2M - dec VWF platelet binding
- 2N - VWF does not carry FVIIIC
- 3- no VWF so severe and early dx; tx w/ VWF conc (auto recessive)
- Dx - if dec APTT (b/c carrier for FVIII so now degraded - prolonged intrinsic path), low VIII, low RCoF, low VWF:Ag and prolonged closure time
2
Q
RCoF
A
- VWF activity is measured by RCoF or the amount of ristocetin it binds
- Larger molecule = more binding sites = inc RCoF = greater chance microthrombus
- Dec RCoF can mean more ADAMTS-13 or plasmin activity, inc binding of platelets so restocetin cannot bind, dec synthesis or release of VWF
3
Q
Normal Role of VWF
A
- VWF is made by endo cells then stored in Weibel-Palade bodies and alpha granules of platelets
- Acts as carrier for FVIII until Xa cleaves it from VWF to be used in intrinsic path
- Released into plasma as large molecule then broken up by ADAMTS-13 enzyme (defective in TTP)
4
Q
Hemophilia
A
- Hemophilia A - FVIII def
- Hemophilia B - FIX def
- Both X-linked
- Same presentation - bleeding w/ circumcision in baby boy; bleed into joints, muscles, body cavities, CNS hemorrhages, hematomas
- Classic - teen male athlete w/ mult “pulled muscles that won’t heal” - actually muscle hematomas
- Degeneration of synovial lining –> crippling OA
- Tx - recombinant factors (worry about formation of inhibitors - T cell immune response against infused factors)
5
Q
FV Leiden Mutation
A
FV lacks protein C cleavage sites so resistant to breakdown of FVa –> inc venous thrombosis
6
Q
Vit K Def (causes and tx)
A
- Fat-soluble; needed for activation of 2, 7, 9, 10, protein S and protein C
- Causes of Deficiency
- Diet
- Hemorrhagic Disease of Newborn - lack of gut bacteria - bleed
- Antibiotics - destroy gut flora that produce Vit K
- Poor GI absorption - obstructive jaundice (no bile salts) or diarrhea/sprue
- Inhibit synthesis - Warfarin, pesticides
- Tx - oral or subQ vit K; Kcentra IV if urgent (all Vit K factors + small amount of heparin); use profilin + recombinant FVII if past HIT
7
Q
How do you screen for Vit K def?
A
- Screen w/ PT b/c FVII has shortest half life (7 hrs) - later both PT and APTT long
8
Q
What are the half-lives of all Vit K dep factors?
A
- VII - 6 hrs
- IX - 24 hrs
- X - 40 hrs
- II - 60 hrs
- Protein C and S - < 6 hrs
9
Q
Liver Disease and Coagulation
A
- Causes dec in synthesis and clearance of factors
- Dec synthesis of coag factors (except VIII - made elsewhere)
- Dec degradation of activated factors - DIC/fibrinolysis
- Synthesis of abnormal factors - dysfibrinogen (takes longer to form clot and friable clot/susceptible to lysis - prolonged TT and RT)
- Platelet Sequestration - thrombocytopenia
- Tx - replace factors w/ fresh frozen plasma, transfuse platelets if thrombocytopenia, if fibrinolysis then use fibrinolytic inhibitors (aminocaproic acid and tranexamic acid)
10
Q
DIC
A
- Excess thrombin generation –> small vessel thrombosis and bleeding; associated w/ consumption of factors, thrombocytopenia, platelet dysfunction, inc fibrinolysis
- Both primary mucosal bleeding and secondary deeper bleeding is seen
- See antithrombin activation –> depletion (anti-thrombin becomes overwhelmed by excess thrombin)
- Fibrinogen –> FDP, FM, FSP which then polymerize –> insoluble fibrin –> creates narrow vessels –> RBC fragments/Burr cells/ schistocytes AND end-organ damage
11
Q
DIC Dx
A
(3/6)
- 1- prolonged PT and/or APTT - 2- dec platelets - 3- dec fibrinogen - 4- Inc fibrin split products - 5- Dec antithrombin - 6- RBC fragmentation
12
Q
5 Poss Causes of DIC
A
- Infection (endotoxin)
- Tissue injury from trauma, surgery, burns (TF)
- OB complications - amniotic fluid embolus or abruptio placenta
- Malignancy -prostate (activates FX), adenocarcinoma (activates trypsin) or promyelocytic leukemia (pro-coagulant material)
- Liver disease - activated coagulation factors not cleared
13
Q
DIC Tx
A
Tx - treat underlying cause + transfusion/replacement of missing elements in meantime
14
Q
Specific Inhibitors v Blocking Inhibitors
A
Specific Inhibitors (RARE)
- Immune inhibition of coagulation factor (auto-immune or allo-immune from transfused factor)
- Bleeding tendency
- Symptoms = severe post-partum bleeding, bleeding in elderly w/o hx, bleeding in hemophilia despite FVIII
Blocking Inhibitors (lupus anti-coagulants)
-Inhibit coagulation REACTIONS (affect mult factors; directed at phospholipids)
-Thrombotic tendency
MORE COMMON (in 5% SLE pts)
-Symptoms = recurrent pregnancy loss, stroke at early age, thrombosis
15
Q
Examples of Specific Inhibitors
A
Anti-VIII - preg and Hemophilia A
Anti-X - amyloidosis
Anti - XIII - isoniazid
Anti-VWF - thryoid disease, lymphoma
