Adhesion, activation and aggregation of platelets is primary homeostasis for clotting.
vWF binds collagen and is regulated by ADAMTS13
Thrombin is regulated by antithrombin and activated Protein C
Fibrin is cleaved by plasmin in degradation products - think D Dimer
Primary - epistaxis, petechiae, bruising and menorrhagia; plt, vwf and vessel wall defects
Secondary - soft tissue bleeds and bleeding into joints; coagulation factors and fibrinogen defects
Menorrhagia, bleeding into joints and bruising
Soft tissue bleeds, and bleeding into joints
Soft tissue bleeds, epistaxis, menorrhagia
Petechiae/bruising, soft tissue bleeds, and bleeding into joints
PT concerns the extrinsic pathway
aPTT concerns the intrinsic pathway. Both concern X, V II (common pathway)
Normal PT is 11-14s
Normal aPTT is 13-24s
Factors VIII, IX, XI, X, V, II
Factors VII, VIII, X, V, II and fibrinogen
Factors X, V, II
Factors VII, fibrinogen
Factor VII, X, V, II
Haemophilia is PAINFUL bleeding, coagulation pathway disorder, mild provoked bleeding if factor missing is <5%; severe, spontaneous bleeding if <1%
Rx is give factor concentrates. Not much else can be done at present
Soft tissue and joint bleeds
Treatment of HCV/HIV
Lifethreatening CNS and GI bleeds
vWD is commonest genetic disorder. Normally mediates plt adhesion and stabilises FVII.
Mild: only one defect. Mild Sx and slightly reduced FVIII but not obvious bleeding
Rx Tranxamic acid (anti fibrinolytic), DDAVP/desmopression, vWF/FVII concentrate
Factor VIII deficiency
Factor VII deficiency
Massively increased PT
Synthesis - Liver, vit K (22.214.171.124) and warfarin
Function - heparin, DOACs, aspirin, antiplt
Dilution - massive transfusion, dilution by fluid, cardiac bypass
Consumption - DIC, TTP in sepsis
Vitamin K malabsorption
If the Pt is stable, no Rx is needed
If Pt is decompensated or BLEEDING, replace EVERYTHING - txa, fibrinogen, vit K, FFP.
DIC has increased APTT and PT and DDIMER. Categorised by massive bleeding and multiorgan failure. Rx is full supportive care, correct the stimulus (e.g sepsis) and aggressively restore homeostasis - give PLT, FFP and fibrinogen conc.
TTP has anti-ADAMTS13 antibodies leading to reduced vWF proteolysis leading to increased mw multimers (hyaline bodies). Agglutinate in high shear vessels with mechanical haemolysis. BLEEDING, often neuro sx, jaundice, pallor and fatigue. RED CELL fragments on blood film. PT and aPTT are usually NORMAL. TROPONIN wil be raised.. Rx is EXCHANGE everything via plasma exchange - plasmaphoresis.
Target cells are thalassaemias
Reed-sternberg are HL
SCFs are SCD
Red cell fragments
Reed sternberg cells
Immediate management is NOT thrombolysis (think stroke/STEMI). Anticoag with heparin/clexane/LMWH followed by warfarin/DOAC long term. No role for aspirin.
Warfarin in pregnancy
Heparin followed by aspirin
Thrombolysis with tPA followed by aspirin
Warfarin and DOAC
Anti-coagulate with heparin and then long-term warfarin/DOAC
ADAMTS13 deficiency is associated with thrombocytopaenia in TTP
FV Leden is caused by reduced activation of FV by Protein C, increased VTE risk by 4x
APLS (antiphospholipid syndrome) is caused by antibodies, either anti CL, antiB2G1 or Lupusanticoag (which may also increase aPTT paradoxically); associated with livedo reticularis, pregnancy loss and thrombocytopaenia. Long term anticoagulaion required if thrombotic events recur. Give DMARDs if underlying SLE.
Anti beta2 glycoprotein 1
Anti coagulants should be used for VTE or low pressure vessel thrombosis. Warfarin/DOACs for valvular clots, enoxaparin for prophylaxis
Anti-platelets should be used in arterial thrombosis.
aspirin, clopidogrel, abixiximab
Rivaroxaban, apixaban, dabigatran
Warfarin has a t1/2 of 36 hours. Reversed by Vitamine K and Factor concentrate if severe bleeding. Stop for 5 days if low risk of VTE prior to surgery, restart one day after. If HIGH risk, need to bridge with LMWH, or UF if very high risk of bleeding.
LMWH has t1/2 of 4-6 hours. Stop if bleeding and give protamine IV. Close INR control of 1.5-2.0 wanted (PT) Last dose for bridging 24 hours before surgery
UF can be given 2-4 hours before surgery as a last dose in high risk patients, as t1/2 is only 1-2 hours.
Rivaroxaban is a Xa inhibitor affecting the extrinsic pathway. Stop 24 hours if normal risk, 48-72 hours before if high risk of bleeding, restart either 6-12 hours after or 48hrs after depending on risk of bleeding. No monitoring routinely, may increase PT/aPTT. Caution in renal impairment. STOP if bleeding and consider specialist products.
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