Bleeding and clotting disorders

  • Created by: MazzaW
  • Created on: 06-12-19 12:40

History and investigations

Bleeding history:

  • easy bruising: spontaneous, minimal trauma, unusual sites
  • gum bleeding
  • prolonged bleeding after minor wounds
  • menorrhagia/postpartum bleeding: iron therapy, blood transfusions, often have had menorrhagia since menarche
  • post-op bleeding: surgery, dental, return to theatre, need for suturing, transfusions
  • bleeding in early childhood
  • FH of a bleeding tendency


  • APTT: assesses intrinsic patthway (factors VIII, IX, XI, XII)- if prolonged, need mixing study (50:50 with normal plasma), if corrects = clotting factor deficiency, if doesn't = inhibitor (most commonly lupus anticoagulant)
  • PT: assesses extrinsic pathway (factor VII)

Vitamin K dependent clotting factors: II, VII, IX, X (1972)

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Haemophilia A

Factor VIII deficiency- only produce a small amount of thrombin (lack of amplification/propagation so no thrombin burst) so can't produce a stable clot

X linked- 1 in 5000 male births

More common than haemophilia B

Characteristic palpable haematomas/bruises, haemarthrosis

Severity classified according to residual factor VIII activity level: >5% = mild, 1-5% = moderate, <1% = severe

Mgmt: recombinant factor VIII concentrate (prophylactic), DDAVP if mild (causes release of vWF from endothelial surface), avaoid aspirin/NSAIDs/heparin, parental education, regular MDT review

Mgmt of haemarthrosis: analgesia, immobilisation of joint, ice pack, physiotherapy

Potential new treatments: esulizumab (monoconal Ab, mimics factor VIII activity, fortnightly SC injection), gene therapy

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Haemophilia B

AKA Christmas disease

X linked factor IX deficiency- only produce small amount of thrombin (no amplification/propagation so no thrombin burst) so can't produce a stable clot

1/5 as common as haemophilia A

Classified as mild/moderate/severe according to factor IX levels

Similar presentation and clinical picture to haemophilia A

Rx: factor IX concentrate, potential new gene therapies arising

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Von Willebrand disease

Commonest inherited bleeding disorder (1 in 1000) with autosomal dominant inheritance

Usually mild bleeding disorder. Occurs due to decreased levels of vWF

Functions of vWF: binds platelets (Gp1b) to subendothelium, platelet binding in high shear stress, binds and stabilises factor VIII

Sx: mucocutaneous bleeding, bruising, post-op bleeding, bleeding from minor wounds, menorrhagia, postpartum bleeding

Ix: decreased factor VIII, decreased vWF antigen, decreased ristocetin cofactor activity

Classification: type 1 (mild quantitative defects- autosomal defects), type 2 (qualitative defects), type 3 (severe quantitative defects, autosomal recessive)

Rx aims to increase circulating levels of vWF: DDAVP (increases vWF release from endothelial surface), pooled plasma concentrates containing vWF

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Other inherited bleeding disorders

Other factor deficiencies: factor XI, factor VII, factor V, factor X, factor XIII

Platelet function disorders: Glanzmann thrombasthenia, Bernard-Soulier syndrome

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Acquired disorders of haemostasis

  • DIC
  • liver disease: decreased production of clotting factors, thrombocytopenia, dysfibrinogenaemia
  • renal disease: abnormal platelet function
  • vitamin K deficiency
  • haemorrhagic disease of the newborn
  • anticoagulants/antiplatelet drugs
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Occurs when balance of procoagulant and anticoagulant factors is overwhelmed by massive systemic procoagulant signal

Causes systemic coagulation and consumption of pro and anticoagulant factors

May present with thrombosis, bleeding or both:

  • oozing from wound sites, IV lines, venepuncture sites and mucosal surfaces
  • petechiae and ecchymoses
  • organ failure secondary to tissue ischaemic injury from intravascular fibrin deposition

Associated with: sepsis, malignancy, trauma (crash injuries, burns), obstetric catastrophe (fetal death, placental abruption, amniotic fluid embolism, pre-eclampsia), liver disease, major haemorrhage, others (incompatible blood transfusion, acute anoxia, extracorporeal circulation)

Dx: clinical, decreased platelets + fibrinogen, increased APTT + PT, increased D-dimers

Mgmt: treat underlying cause, resuscitation, blood product replacement therapy (red cells, platelets, FFR, cryoprecipitate)

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Risk factors for clotting

  • previous VTE (DVT, PE, cerebral sinus thrombosis, mesenteric vein thrombosis)
  • AF
  • arterial embolus/thrombosis
  • metallic heart valves
  • ventricular assist devices
  • antiphospholipid syndrome
  • increasing age
  • pregnancy
  • immobilisation
  • surgery
  • malignancy
  • air travel
  • oestrogen (oral contraception, HRT)
  • thrombophilia
  • polycythaemia
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Tendency to clot

Protein C, protein S and antithrombin are all naturally occurring anticoagulants- deficiency of any of these leads to a tendency to clot

Factor V Leiden: point mutation in factor V gene leads to slowing of inactivation of favtor Va so have a tendency to form clots. Common in the general population (5% in UK, becomes more common the further north in Europe you go)

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Mostly DVT and PE. Present in 20% post-mortems but usually non-fatal- most deaths related to comorbid condition. Can have chronic problems following VTE (pulmonary hypertension after PE, venous insufficiency/ulcers following DVT)

All hospitalised patients should be assessed for risk of VTE and considered for thromboprophylaxis (anti-embolic stockings, early mobilisation, mechanical/pharmaceutical prophylaxis)

Well's score (DVT probability): +1 for paralysis/paresis/plaster/immobilisation of lower limbs, bedridden for 3+ days/major surgery in last 5wks/uninterrupted travel >3hrs in last 5wks, active cancer/Rx in last 6 months, entire leg swollen, calf swelling >3cm, tenderness along deep veins, pitting oedema worse in affected leg, collateral superficial veins (not varicose). -2 if alternative Dx more likely

Negative D-dimer rules out VTE (establish alternative Dx before referral back to GP) but D-dimer has poor PPV. 

If high risk/positive D-dimer: Doppler USS (if DVT), CXR then CTPA or V/Q scan (if no DVT but PE suspected). If positive, treat (outpatient if possible). If negative, establish alternative Dx before referral back to GP

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Warfarin- inhibits vitamin K reductase (prevents recycling of vitamin K)- affects factors II, VII, IX + X. Also inhibits proteins C + S so while it has a net anticoagulant effect, can be difficult to predict (need regular INR monitoring)

DOACs- more predictable + do not need monitoring. Not always suitable in people at very high risk of clotting/bleeding. Include factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) and direct thrombin inhibitors (dabigatran). 

Standard anticoagulation for acute VTE:

  • LMWH for at least 5 days
  • then move onto warfarin: 5mg for 1st 2 days then check INR and adjust dose accordingly
  • continue INR monitoring for duration of treatment
  • OR: start on DOAC
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Reversal of anticoagulation

Not all DOACs can be reversed but antidotes are being found (e.g. idarucizumab for dabigatran)

Reversal or over-warfarinisation (should have INR of 2-3):

  • major bleeding: omit warfarin, plasma complex concentrate (e.g. Beriplex) and IV vitamin K
  • minor bleeding/very high risk (INR >8): omit warfarin, IV vitamin K, may need fresh frozen plasma
  • just high INR: omit warfarin, vitamin K replacement (IV if high risk, PO if low risk)

Anticoagulant-associated intracranial haemorrhage: rapid deterioration in 1st 24-48hr with raised intracranial haemorrhage volume. Poor outcomes associated with ICH volume and intraventricular extension of bleeding.Majority occurs with INR of 2-3.5. Rapid reversal of anticoagulation essential to prevent haematoma expansion and allow for surgical intervention.

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