Module 4 Flashcards
What are the causes of a prolonged thrombin clotting time?
Heparin Dabigatran Dysfibrinogenaemia Fibrin degradation products (DIC) Liver disease
What are some acquired causes of thrombocytopenia?
Immune: ITP, SLE, malignancy associated antibodies
Drug induced: quinines, sulphurs, heparins
Viruses: EBV/HIV
Post-transfusion alloimmunity
TTP
DIC
Sequestration in splenomegaly
Decreased production eg: bone marrow failure, aplastic anaemia, alcohol toxicity
What is the pathophysiology of TTP?
Congenital or acquired deficiency of ADAMTS13 (vWF cleaving enzyme)
Platelets aggregate, activate and self-consume
Fragemetary haemolysis and microvascular thrombosis
What are some acquired causes of platelet DYSFUNCTION?
- myelodysplasia: adequate number but they’re dysfunctional
- myeloproliferative: over-production
- uraemia
- drugs
- diet: garlic, ginko, ginger
How is vit K metabolised in the gut?
What is its role in coagulation?
What does warfarin do to change this?
- Dietary Vit K is protein bound and released by pancreatic enzymes
- Bile salts solubilize, incorporated into chylomicrons and transported to liver
- Assists in carboxylation of II, VII, IX and X which assists in localisation to phospholipid
- Warfarin blocks reduction of Vit K epoxide back to vit K, preventing it from γ carboxylation of coagulation factors
What are some causes of reduced clotting factors?
IMPAIRED PRODUCTION
- liver disease
- vit K deficiency
INCREASED DESTRUCTION
- DIC
- MTF
- inhibitors
DYSFUNCTION
- anticoagulant meds
Differentiate between causes of palpable and non-palpable purpurae
Palpable purpura: fibrin activation within subcutaneous tissue
Vasculitis
Allergic
Non-palpable: red cell leakage into tissues due to reduced integrity of connective tissue
Small bruises
Senile
What are some of the key effects of sepsis on coagulation?
○ Increased leucocyte adhesion ○ Shift to procoagulant state ○ Vasodilation ○ Loss of barrier function ○ Microthrombi due to plugs of WBC and RBC
TF exposure, fibrin deposition and impaired activated protein C can produce DIC
What is the role of PAR1 and its link between coagulation and inflammation?
Protease-activated receptors (PAR1)
- PAR1 cytoprotective when stimulated by activated protein-C or low-dose thrombin
- With High dose thrombin, disrupts endothelial cell barrier function
Describe the pathophysiology of acute/decompensated DIC
- Blood exposed to acute increased tissue factor or procoagulants
- Rapid consumption of coagulation factors
- FDPs disrupt normal fibrin polymerisation, clot formation and platelet aggregation
- Severe bleeding diathesis –> prolonged clotting times
Describe the pathophysiology of chronic/compensated DIC
- Continuous exposure to tissue factor/procoagulant
- Coag factors/platelets consumed but compensate with production
- Liver clears FDPs
- Normal clotting times, mild thrombocytopenia or normal
- Thrombosis > bleeding
What are the diagnostic criteria for DIC?
Plt: <100 1 pt, <50 2 pts
PT: 3-6 1 pt, >6 2 pt
Fibrinogen: <1 1 pt
d-dimer: moderate increase, 1 pt, strong increase 2 pt
<5 non-overt DIC, repeat testing in 1-2 days
What are the indications for treatment in DIC?
- Active bleeding
- Require invasive procedures
- High risk for bleeding complications
What is the management of DIC?
TREAT UNDERLYING CAUSE
- transfuse to plt >50
- supplement FFP to correct PT/APTT
- cryp + FFP to fibrinogen >1
- avoid prothrombinex
- LMWH prophylaxis
- if clots, therapeutic heparin/LMWH
What are the PRO-haemostatic changes in chronic liver disease?
PRIMARY
- low ADAMTS13
- elevated vWF
SECONDARY
- Low protein C, protein S, antithrombin, heparin cofactor II
- elevated fVIII
FIBRINOLYSIS
- low plasminogen
