Haematology: Haemostasis and Thrombosis

🩹 Haemostasis is a balance between bleeding and clotting. Too far one way causes bruising and haemorrhage; too far the other causes DVT, PE and stroke. Anticoagulants are among the drugs most often linked to harm in hospital, so using them safely is a core skill. Pulmonary embolism is covered in the Respiratory chapters, and TTP and DIC in the Haematological Emergencies chapter.
Your four questions for every patient: Is the bleeding pattern from platelets or from clotting factors? What do the platelet count, PT and APTT show? For a clot - was it provoked, and how long should treatment last? Is the anticoagulant, dose and kidney function right for this patient?

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Approach to Bleeding and Clotting Tests

Bleeding history:

• Easy bruising; nosebleeds; gum bleeding.
• Heavy periods; bleeding after childbirth.
• Bleeding after dental extraction or surgery.
• Bleeding into joints or muscles.
• Family history.
• Drugs - anticoagulants, antiplatelets, NSAIDs, SSRIs, herbal remedies (ginkgo, fish oils).
• Liver and kidney disease.
• A structured bleeding score (e.g. ISTH-BAT) helps.

Two patterns:

• Platelet or vessel type (low platelets, VWD) - skin and mucosa: petechiae, purpura, nosebleeds, gum bleeding, heavy periods. Bleeding starts immediately after injury.
• Clotting factor type (haemophilia) - deep bleeding into joints and muscles; bleeding may be delayed after injury or surgery.

Interpreting clotting tests:

Result	Common causes
PT (INR) prolonged only	Warfarin, vitamin K deficiency (poor diet, malabsorption, antibiotics, obstructive jaundice), early liver disease, factor VII deficiency
APTT prolonged only	Unfractionated heparin, haemophilia A or B, von Willebrand disease, factor XI deficiency, lupus anticoagulant (a clotting risk, not bleeding), factor XII deficiency (no bleeding), acquired haemophilia
Both PT and APTT prolonged	DIC, liver disease, warfarin excess, massive transfusion, DOACs (variable), severe vitamin K deficiency
Low fibrinogen	DIC, major haemorrhage, liver failure, thrombolysis, inherited
Normal tests but bleeding	Platelet function problems (aspirin, clopidogrel, uraemia), mild VWD, factor XIII deficiency, vessel disorders (Ehlers–Danlos, scurvy, steroids)

• Mixing study: If a prolonged test corrects when mixed with normal plasma, a factor is missing. If it doesn't correct, an inhibitor is present (lupus anticoagulant, acquired haemophilia).
• DOACs affect tests unpredictably - anti-Xa levels (drug-calibrated) or dabigatran levels measure them if needed.

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Approach to Low Platelets

First, exclude pseudothrombocytopenia - platelets clump in EDTA tubes. Check the film and repeat in a citrate tube.

Causes:

• Reduced production:
  • Marrow failure or infiltration (leukaemia, MDS, aplastic anaemia, cancer).
  • B12 or folate deficiency.
  • Alcohol.
  • Chemotherapy.
  • Viruses (HIV, hepatitis C).
• Increased destruction:
  • ITP.
  • Drugs - heparin (HIT), quinine, linezolid, valproate, co-trimoxazole, piperacillin, vancomycin, GP IIb/IIIa inhibitors.
  • SLE; antiphospholipid syndrome.
  • Post-transfusion purpura.
• Consumption: DIC, TTP, HUS, sepsis, HELLP syndrome, major bleeding.
• Sequestration: Hypersplenism (portal hypertension).
• Pregnancy: Gestational thrombocytopenia (mild, usually over 70 × 10⁹/L, late pregnancy, harmless); also pre-eclampsia, HELLP, ITP.
• Dilution: Massive transfusion.

How worried to be:

• Over 50 × 10⁹/L - spontaneous bleeding is rare.
• Under 20 - risk of bleeding rises.
• Under 10 - risk of serious spontaneous bleeding.
• Urgent same-day referral: Platelets under 20, active bleeding, other abnormal counts or blasts, or schistocytes (TTP).

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Immune Thrombocytopenia

What it is: Antibodies destroy platelets, and also reduce their production. It causes isolated thrombocytopenia (other counts and the film are normal). It is a diagnosis of exclusion.

• Children: Often follows a viral infection; sudden bruising and petechiae; usually resolves within weeks to months without treatment.
• Adults: More often chronic (over 12 months); commoner in women.
• Secondary causes to look for:
  • HIV, hepatitis C, H. pylori.
  • SLE; antiphospholipid syndrome.
  • CLL and lymphoma.
  • Drugs.
  • Common variable immunodeficiency.
  • Pregnancy.
• Features: Petechiae, purpura, nosebleeds, gum bleeding, heavy periods. Many have no symptoms. Serious bleeding (e.g. intracranial) is rare. No splenomegaly.
• When to treat: Bleeding, or platelets under about 20–30 × 10⁹/L, or before procedures - not the count alone.
• First line:
  • Prednisolone 1 mg/kg (short course, then taper), or dexamethasone 40 mg daily for 4 days.
  • IVIg for a rapid rise (severe bleeding, before surgery).
• Second line:
  • Thrombopoietin receptor agonists - eltrombopag, romiplostim, avatrombopag.
  • Rituximab.
  • Fostamatinib.
  • Mycophenolate.
  • Splenectomy (less common now; vaccinate first).
• Life-threatening bleeding:
  • IV methylprednisolone, IVIg, platelet transfusion (short-lived benefit), tranexamic acid.
  • Stop antiplatelets and NSAIDs.
• Pregnancy: Steroids or IVIg; plan delivery. The baby may be born with low platelets.

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Heparin-induced Thrombocytopenia

What it is: An immune reaction to heparin. Antibodies against heparin–platelet factor 4 (PF4) complexes activate platelets. This causes thrombocytopenia - and, paradoxically, thrombosis (arterial and venous).

• Timing: Platelets fall 5–10 days after starting heparin (sooner if heparin was given in the last 3 months).
• Features:
  • Platelets fall by more than 50% (usually not below 20).
  • New thrombosis - DVT, PE, limb ischaemia, stroke.
  • Skin necrosis at injection sites.
  • Reactions to IV heparin.
• Risk: Higher with unfractionated heparin than LMWH, and after surgery (especially cardiac and orthopaedic).
• Assess probability with the 4Ts score:
  • Thrombocytopenia.
  • Timing.
  • Thrombosis.
  • oTher causes.
  • If intermediate or high - test for anti-PF4 antibodies.
• Management (if intermediate or high probability, don't wait for results):
  • Stop all heparin - including flushes and heparin-coated lines.
  • Start a non-heparin anticoagulant at treatment dose (even without thrombosis) - argatroban, danaparoid, fondaparinux, or a DOAC.
  • Don't give platelets (they fuel thrombosis) unless bleeding is life-threatening.
  • Don't start warfarin until platelets recover (risk of skin necrosis and limb gangrene).
  • Scan the legs for silent DVT.
  • Record heparin allergy prominently.
• Related condition: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) - after adenoviral vector COVID-19 vaccines; similar anti-PF4 antibodies.

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Haemophilia

What it is: An inherited deficiency of a clotting factor.

• Haemophilia A - factor VIII (about 5 in 6 cases).
• Haemophilia B - factor IX.
• X-linked recessive - affects males; female carriers can have low levels and bleed.

Severity by factor level:

• Severe (under 1%) - spontaneous bleeding into joints and muscles.
• Moderate (1–5%) - bleeding after minor injury.
• Mild (5–40%) - bleeding after surgery or major trauma; may be diagnosed late.

Features:

• Haemarthroses (knees, elbows, ankles) - lead to chronic joint damage.
• Muscle haematomas - iliopsoas bleeds cause hip flexion and femoral nerve compression.
• Bleeding after circumcision, dental work or surgery.
• Intracranial haemorrhage.

Tests:

• Prolonged APTT, normal PT and platelets.
• Low factor VIII or IX.
• Exclude VWD (which can also lower factor VIII).

Treatment (at a haemophilia centre):

• Factor replacement - recombinant factor VIII or IX (standard or extended half-life) for bleeds and as regular prophylaxis in severe disease.
• Emicizumab - a weekly to monthly subcutaneous antibody that mimics factor VIII, used as prophylaxis in haemophilia A.
• Gene therapy - available for selected adults (e.g. haemophilia B).
• Desmopressin - raises factor VIII in mild haemophilia A (fluid restriction afterwards - hyponatraemia risk).
• Tranexamic acid for mouth and nose bleeding.
• Inhibitors (antibodies against the factor) - bypassing agents (recombinant factor VIIa, FEIBA) or emicizumab.

Important rules:

• Treat any suspected bleed promptly - "factor first", before scans.
• Head injury in haemophilia - give factor, then image.
• Avoid IM injections, NSAIDs and aspirin.
• Patients carry treatment cards and often their own factor.

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Von Willebrand Disease

What it is: The commonest inherited bleeding disorder (up to 1 in 100 have low levels; about 1 in 10,000 have significant symptoms). Von Willebrand factor helps platelets stick, and carries factor VIII.

Types:

• Type 1 - partial shortage (mild; autosomal dominant; about 75%).
• Type 2 - abnormal function.
• Type 3 - almost none (severe, recessive; low factor VIII causes joint bleeds too).

Features:

• Mucocutaneous bleeding - nosebleeds, easy bruising, gum bleeding.
• Heavy menstrual bleeding (a common presentation - test women with heavy periods since menarche).
• Postpartum haemorrhage.
• Bleeding after dental extraction or surgery.

Tests:

• VWF antigen and activity; factor VIII.
• APTT may be normal or prolonged.
• Levels rise with stress, pregnancy, inflammation and the pill - repeat if normal but suspicion is high.
• Blood group O has lower levels.

Treatment:

• Tranexamic acid (heavy periods, dental work).
• Desmopressin (type 1) - test response first; restrict fluids (hyponatraemia).
• VWF-containing concentrates (type 2, 3, major surgery).
• Hormonal treatment for heavy periods (LNG-IUS).
• Avoid NSAIDs and aspirin.

Acquired VWD: Aortic stenosis (Heyde's syndrome - GI bleeding), LVADs, MGUS and lymphoproliferative disease, hypothyroidism.

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Other Bleeding Disorders

• Vitamin K deficiency:
  • Causes:
    • Newborns - vitamin K deficiency bleeding; all babies are offered vitamin K at birth.
    • Poor intake (critical illness, malnutrition).
    • Antibiotics.
    • Malabsorption and obstructive jaundice (fat-soluble vitamin).
  • Prolonged PT that corrects with IV vitamin K within 6–24 hours (unlike liver failure).
• Liver disease:
  • Low clotting factors, but also low natural anticoagulants ("rebalanced").
  • The INR doesn't predict bleeding well.
  • Low platelets and fibrinogen matter more.
  • See the Cirrhosis chapter.
• Acquired haemophilia A:
  • Autoantibodies against factor VIII, usually in older people, or postpartum, with cancer or autoimmune disease.
  • Sudden extensive bruising and muscle bleeds in someone with no bleeding history.
  • Isolated prolonged APTT that doesn't correct with mixing.
  • Haematology emergency - bypassing agents and immunosuppression (steroids, rituximab).
• Platelet function disorders:
  • Drugs - aspirin, clopidogrel, NSAIDs, SSRIs.
  • Uraemia (desmopressin helps).
  • Inherited (rare) - Glanzmann thrombasthenia, Bernard–Soulier syndrome.
• Vessel wall and connective tissue:
  • Senile purpura (older skin).
  • Steroid use.
  • Scurvy (vitamin C - perifollicular bleeding, gum bleeding).
  • Ehlers–Danlos syndrome.
  • Hereditary haemorrhagic telangiectasia.
  • Amyloidosis (periorbital purpura).
  • IgA vasculitis (palpable purpura on the legs and buttocks).
• Non-accidental injury - consider in children and vulnerable adults with unexplained bruising.

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Diagnosing DVT

Risk factors for VTE:

• Recent surgery (especially orthopaedic), hospital admission, immobility, long travel.
• Active cancer and chemotherapy.
• Pregnancy and the postpartum period; the combined pill and HRT (oral).
• Previous VTE; family history; thrombophilia.
• Obesity; older age.
• IBD; nephrotic syndrome; infection (including COVID-19).
• Central lines.

Assessment of suspected DVT (NICE NG158):

• Symptoms: Unilateral leg swelling, pain, tenderness, warmth, pitting oedema, dilated veins.
• Two-level DVT Wells score:
  • DVT likely (2 or more) - proximal leg vein ultrasound within 4 hours. If not possible, do a D-dimer and give an interim anticoagulant (e.g. apixaban or rivaroxaban) while waiting for a scan within 24 hours.
  • DVT unlikely (1 or less) - D-dimer. If positive, ultrasound; if negative, consider other diagnoses.
  • If ultrasound is negative but D-dimer positive and DVT is likely - repeat ultrasound in 6–8 days.
• D-dimer is sensitive but not specific - raised in older age, pregnancy, infection, cancer and after surgery. An age-adjusted threshold can be used for people over 50.
• Differential diagnosis: Cellulitis, ruptured Baker's cyst, muscle injury, lymphoedema, heart failure, superficial thrombophlebitis.
• Pulmonary embolism - see the Respiratory Emergencies and Pulmonary Vascular chapters.

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Treating Venous Thromboembolism

Choice of anticoagulant (NICE NG158):

• Apixaban or rivaroxaban first line (no initial heparin needed):
  • Apixaban 10 mg twice daily for 7 days, then 5 mg twice daily.
  • Rivaroxaban 15 mg twice daily for 21 days, then 20 mg once daily (with food).
• Alternatives: LMWH for at least 5 days followed by dabigatran or edoxaban; or LMWH with warfarin (until INR is 2 or more for 2 days).
• LMWH is preferred or required in:
  • Pregnancy.
  • Severe kidney failure (or unfractionated heparin).
  • Extremes of body weight (check levels).
  • Some cancers (e.g. GI or urothelial with high bleeding risk).
  • Significant drug interactions.
• Warfarin (INR target 2.5) for antiphospholipid syndrome, mechanical valves, and when DOACs are unsuitable (e.g. creatinine clearance under 15 mL/min).

How long to treat:

• Provoked VTE (clear temporary risk factor such as surgery): 3 months (3–6 months for proximal DVT or PE).
• Unprovoked VTE: 3 months, then consider long-term anticoagulation if the bleeding risk is low - balance recurrence risk (about 10% in the first year after stopping) against bleeding risk (e.g. using ORBIT), and the patient's preference.
• Cancer-associated VTE: 3–6 months or longer while the cancer is active.
• Recurrent VTE: Usually long-term.
• Review at 3 months, then at least yearly if long-term.

Other points:

• Don't routinely screen for cancer after unprovoked VTE beyond history, examination and basic tests (FBC, U&E, LFTs, calcium, urinalysis, chest X-ray if indicated) - NICE 2020.
• Thrombophilia testing is not routine (see below).
• Compression stockings aren't recommended routinely to prevent post-thrombotic syndrome; use them for symptoms.
• IVC filters only if anticoagulation is contraindicated in acute VTE (remove later).
• Distal (calf) DVT - treat if symptomatic, or repeat the scan at 1 week to check for extension.
• Superficial vein thrombosis - NSAIDs and compression. Fondaparinux 2.5 mg daily for 45 days if 5 cm or longer, or near the saphenofemoral junction (within 3 cm - then scan, as it may need full treatment).

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VTE in Special Situations

• Cancer-associated thrombosis:
  • DOAC (apixaban, rivaroxaban, edoxaban) or LMWH.
  • Use LMWH where there is high GI or urinary bleeding risk, or interactions with chemotherapy.
  • Continue while the cancer is active.
• Pregnancy and postpartum:
  • LMWH (weight-based dose) for the rest of pregnancy and at least 6 weeks postpartum (3 months total minimum).
  • DOACs and warfarin are avoided in pregnancy.
  • Warfarin and LMWH are safe in breastfeeding.
  • Plan delivery around LMWH (epidural timing).
• Kidney impairment:
  • Calculate creatinine clearance (Cockcroft–Gault) with actual body weight.
  • Avoid most DOACs under 15 mL/min (dabigatran under 30).
  • Use unfractionated heparin or dose-adjusted LMWH with anti-Xa monitoring.
• Unusual-site thrombosis:
  • Cerebral venous sinus (see the Stroke chapter).
  • Splanchnic veins (portal, mesenteric, hepatic).
  • Test for myeloproliferative neoplasms (JAK2) and PNH, as well as antiphospholipid syndrome.
• Upper limb DVT:
  • Usually linked to central lines or pacemaker leads, or cancer.
  • Paget–Schroetter syndrome - effort thrombosis in young athletes (thoracic outlet).
  • Treat for 3 months; a line can stay in if it is needed and working.
• Older and frail patients: Falls alone are not a reason to withhold anticoagulation; review doses with weight and kidney function.

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Preventing VTE in Hospital

Hospital-acquired thrombosis is a major preventable cause of death (NICE NG89).

• Assess every patient on admission (and when their condition changes) for VTE risk and bleeding risk.
• Medical patients:
  • LMWH (e.g. enoxaparin 40 mg once daily; 20 mg if creatinine clearance is under 30), or fondaparinux, for at least 7 days if risk outweighs bleeding risk.
  • Encourage mobilisation and hydration.
• Surgical patients:
  • Mechanical prophylaxis (anti-embolism stockings or intermittent pneumatic compression) plus LMWH as appropriate.
  • Extended prophylaxis:
    • Hip replacement - LMWH for 10 days then aspirin for 28 days, or LMWH or a DOAC for 28–35 days.
    • Knee replacement - aspirin for 14 days, or LMWH or a DOAC.
    • Major cancer surgery in the abdomen or pelvis - LMWH for 28 days.
• Stroke patients: Intermittent pneumatic compression (not stockings) for immobile patients.
• Lower limb plaster casts: Consider LMWH while immobilised.
• Pregnancy: RCOG risk assessment antenatally and postnatally.
• Contraindications to LMWH:
  • Active bleeding.
  • Platelets under 50.
  • Recent brain or eye surgery.
  • Severe uncontrolled hypertension.
  • Bleeding disorders.
  • Spinal procedures within certain timeframes.
• Stockings are contraindicated in peripheral arterial disease, severe neuropathy and leg ulcers.

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Thrombophilia and Antiphospholipid Syndrome

Inherited thrombophilias:

• Factor V Leiden - the commonest (about 5% of white Europeans); modest increase in risk.
• Prothrombin gene mutation (G20210A).
• Protein C, protein S and antithrombin deficiency - rarer, higher risk. Protein C deficiency can cause warfarin-induced skin necrosis.

When to test (NICE NG158 and BSH) - not routinely:

• Don't test people with provoked VTE, or those who will continue anticoagulation anyway - results rarely change management.
• Consider antiphospholipid antibody testing in unprovoked VTE if stopping anticoagulation is planned (it changes treatment).
• Consider hereditary testing in unprovoked VTE with a first-degree relative who has had VTE, if stopping anticoagulation is planned.
• Don't test during acute thrombosis or on anticoagulants (results are unreliable).

Antiphospholipid syndrome (APS):

• Clinical features:
  • Venous or arterial thrombosis (stroke at a young age).
  • Pregnancy complications - recurrent early miscarriage, late fetal loss, severe pre-eclampsia, placental insufficiency.
  • Livedo reticularis; low platelets; heart valve lesions.
• Laboratory criteria: Lupus anticoagulant, anticardiolipin, or anti-beta2 glycoprotein I antibodies - positive on two occasions at least 12 weeks apart.
• Primary or secondary (with SLE).
• Treatment:
  • Warfarin long-term after thrombosis (INR 2–3; higher for some arterial events).
  • DOACs are not recommended, especially in "triple-positive" APS or arterial disease (more clots).
  • Pregnancy: Low-dose aspirin plus LMWH (prophylactic or treatment dose depending on history); stop warfarin before 6 weeks.
• Catastrophic APS: Rapid multi-organ thrombosis - ICU, anticoagulation, steroids, plasma exchange or IVIg.

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Using Anticoagulants Safely

Drug	Key points
Apixaban (Xa inhibitor)	AF: 5 mg twice daily; 2.5 mg twice daily if 2 of: age 80 or over, weight 60 kg or less, creatinine 133 µmol/L or more. VTE: 10 mg twice daily for 7 days, then 5 mg twice daily
Rivaroxaban (Xa inhibitor)	AF: 20 mg once daily with food (15 mg if CrCl 15–49). VTE: 15 mg twice daily for 21 days, then 20 mg daily
Edoxaban (Xa inhibitor)	60 mg daily (30 mg if CrCl 15–50, weight 60 kg or less, or certain interacting drugs). After 5 days of LMWH for VTE
Dabigatran (thrombin inhibitor)	Mostly cleared by the kidneys - avoid if CrCl under 30. Dyspepsia. Reversal agent: idarucizumab
Warfarin (vitamin K antagonist)	INR target 2.5 (range 2–3) for most; 3.0–3.5 for some mechanical valves (mitral) and recurrent VTE despite good control. Many interactions (antibiotics, azoles, amiodarone, alcohol). Required for mechanical valves and APS - DOACs are contraindicated for mechanical valves
LMWH (enoxaparin, dalteparin, tinzaparin)	Weight-based; reduce in severe kidney impairment; monitor platelets if exposed to unfractionated heparin recently (HIT); anti-Xa levels in pregnancy, kidney failure or extremes of weight
Unfractionated heparin	IV infusion with APTT monitoring; short-acting, fully reversed by protamine - useful in kidney failure, high bleeding risk, or around procedures

Safety checklist for DOACs:

• Calculate creatinine clearance (Cockcroft–Gault, actual body weight) - don't rely on eGFR alone, especially in older or underweight patients.
• Correct dose for the indication - under-dosing is common and increases stroke risk.
• Interactions - avoid with strong enzyme inducers (rifampicin, carbamazepine, phenytoin, St John's wort) and some HIV and antifungal drugs. Caution with other drugs that increase bleeding (NSAIDs, SSRIs, antiplatelets).
• Check FBC, U&E and LFTs at least yearly (more often in kidney impairment or older age).
• Educate patients - adherence (short half-life), missed doses, alert card, bleeding signs.

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Bleeding on Anticoagulants

• All major bleeding:
  • Resuscitate; stop the anticoagulant.
  • Note the time of the last dose; check FBC, clotting and kidney function.
  • Tranexamic acid (except in GI bleeding, where it doesn't help and raises VTE risk).
  • Treat the source (endoscopy, surgery, embolisation).
• Warfarin:
  • Major bleeding - prothrombin complex concentrate (PCC, e.g. 25–50 units/kg) plus IV vitamin K 5–10 mg. FFP only if PCC isn't available.
  • INR over 8, no bleeding - stop warfarin; oral vitamin K 1–5 mg; restart when INR is under 5.
  • INR 5–8, no bleeding - withhold 1–2 doses and reduce the maintenance dose. Minor bleeding - also give IV vitamin K 1–3 mg.
  • Find the cause of the high INR (interactions, illness, alcohol, diet).
• Dabigatran - idarucizumab (specific antidote) for life-threatening bleeding or urgent surgery; haemodialysis can remove it.
• Factor Xa inhibitors (apixaban, rivaroxaban, edoxaban):
  • Andexanet alfa - NICE recommends it only for life-threatening GI bleeding on apixaban or rivaroxaban (TA697).
  • Otherwise use PCC (off-label).
  • Activated charcoal if taken within 2–6 hours.
• Heparin - protamine fully reverses unfractionated heparin and partly reverses LMWH.
• Restarting:
  • Restart when bleeding is controlled and the indication is strong (e.g. AF with high stroke risk) - often within 1–2 weeks after GI bleeding.
  • Longer after intracranial haemorrhage (specialist decision).
  • Stopping permanently often carries more risk than restarting.
• See the Haematological Emergencies and Stroke chapters for major haemorrhage and anticoagulant-related brain bleeds.

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Antiplatelet Drugs and Bleeding

• Aspirin - irreversible COX inhibition; the effect lasts the platelet lifespan (7–10 days).
• P2Y12 inhibitors - clopidogrel, prasugrel (irreversible), ticagrelor (reversible; also causes breathlessness).
• Dual antiplatelet therapy after ACS or stents - duration decided by cardiology; adding an anticoagulant ("triple therapy") greatly raises bleeding risk, so keep it short.
• Gastroprotection - PPI for people on antiplatelets with GI risk factors (lansoprazole or pantoprazole with clopidogrel).
• Before procedures - see the GI Investigations and Cardiology Special Situations chapters. Never stop antiplatelets after a recent stent without cardiology advice.
• Bleeding on antiplatelets: Stop if possible; platelet transfusion only for life-threatening bleeding or neurosurgery (limited evidence; it can be harmful in ICH on antiplatelets unless surgery is needed).

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Drug Reference Table

Drug	Key points
Apixaban VTE: 10 mg twice daily for 7 days, then 5 mg twice daily	First-line VTE; AF 5 mg twice daily (2.5 mg if 2 criteria); check CrCl.
Rivaroxaban VTE: 15 mg twice daily for 21 days, then 20 mg daily	Take with food; AF 20 mg (15 mg if CrCl 15–49).
Enoxaparin Prophylaxis 40 mg daily; treatment 1.5 mg/kg daily	Reduce if CrCl under 30; anti-Xa monitoring in pregnancy and extremes of weight.
Warfarin	INR 2–3 (target 2.5); APS and mechanical valves; many interactions.
Fondaparinux 2.5 mg daily	Superficial vein thrombosis (45 days); HIT alternative.
Argatroban	IV direct thrombin inhibitor for HIT; APTT monitoring.
Prednisolone / dexamethasone	ITP first line (prednisolone 1 mg/kg or dexamethasone 40 mg for 4 days).
IVIg	ITP with bleeding or before surgery - rapid rise.
Eltrombopag / romiplostim / avatrombopag	TPO receptor agonists - second-line ITP; aplastic anaemia (eltrombopag).
Desmopressin	Mild haemophilia A, type 1 VWD, uraemic bleeding; restrict fluids (hyponatraemia).
Tranexamic acid	Mucosal bleeding, heavy periods, trauma, surgery; not in GI bleeding.
Emicizumab	Subcutaneous prophylaxis in haemophilia A.
Prothrombin complex concentrate + vitamin K IV	Major bleeding on warfarin.
Idarucizumab	Reverses dabigatran.
Andexanet alfa	Life-threatening GI bleeding on apixaban or rivaroxaban (NICE TA697).
Protamine	Reverses unfractionated heparin (partial for LMWH).

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Spot the Diagnosis

Clue	Diagnosis
Platelets 30 with clumps on the film, no bleeding	Pseudothrombocytopenia (EDTA)
Petechiae after a viral illness in a 4-year-old; platelets 8, otherwise normal	ITP (childhood)
Platelets fall from 280 to 90 on day 7 of heparin, new DVT	Heparin-induced thrombocytopenia
Boy with swollen knee after minor fall, APTT prolonged, PT normal	Haemophilia A or B
Woman with heavy periods since menarche and nosebleeds, low VWF	Von Willebrand disease
80-year-old with sudden large bruises, isolated APTT prolongation not correcting on mixing	Acquired haemophilia A
Prolonged PT correcting after IV vitamin K in a patient with obstructive jaundice	Vitamin K deficiency
Prolonged APTT, no bleeding, recurrent miscarriages	Antiphospholipid syndrome (lupus anticoagulant)
Painful skin necrosis days after starting warfarin without heparin cover	Warfarin-induced skin necrosis (protein C deficiency)
Arm swelling in a young weightlifter	Paget–Schroetter syndrome (effort thrombosis)
Portal vein thrombosis with normal blood count in a 40-year-old	Test for JAK2 (masked MPN) and PNH
GI bleed on apixaban 5 mg twice daily in an 85-year-old weighing 52 kg	DOAC overdosing (should be 2.5 mg twice daily)
INR 9 after a course of clarithromycin, no bleeding	Warfarin interaction - oral vitamin K, withhold
Recurrent GI bleeding with aortic stenosis	Heyde's syndrome (acquired VWD with angiodysplasia)

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Exam-style Scenarios

1. A 56-year-old has a swollen right calf. Wells score is 3. Ultrasound can't be done until tomorrow.
Answer: DVT likely.

• D-dimer and an interim anticoagulant (e.g. apixaban 10 mg twice daily).
• Proximal leg ultrasound within 24 hours.
• If confirmed: continue apixaban; decide duration based on whether it was provoked.

2. A 45-year-old has a first unprovoked PE. After 3 months of apixaban she is well. Bleeding risk is low.
Answer: Consider long-term anticoagulation.

• Discuss recurrence vs bleeding risk.
• Consider antiphospholipid antibody testing if stopping is being considered.
• If continuing: apixaban 5 mg (or 2.5 mg) twice daily long-term, with yearly review.

3. A 70-year-old on day 8 of IV unfractionated heparin after cardiac surgery has platelets 60 (from 250) and a new arterial clot in the leg.
Answer: High 4Ts score - HIT with thrombosis.

• Stop all heparin (including flushes); start argatroban; send anti-PF4 antibodies.
• No platelet transfusion; no warfarin until platelets recover.
• Vascular surgery review; record heparin allergy.

4. An 82-year-old on warfarin for AF has a large GI bleed. INR is 4.2.
Answer: Major bleeding on warfarin.

• Resuscitate; stop warfarin.
• PCC plus IV vitamin K 5–10 mg; urgent endoscopy.
• Plan to restart anticoagulation once bleeding is controlled (consider a DOAC at the correct dose).

5. A 30-year-old woman has platelets of 15 × 10⁹/L, petechiae and gum bleeding. FBC and film are otherwise normal.
Answer: Probable ITP.

• Test HIV, hepatitis C, H. pylori; check for SLE and pregnancy.
• Prednisolone 1 mg/kg or dexamethasone 40 mg for 4 days; IVIg if bleeding significantly.
• Avoid NSAIDs; second-line TPO receptor agonists if it persists.

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Key Points

• Platelet-type bleeding affects skin and mucosa; factor-type bleeding affects joints and muscles.
• Isolated prolonged APTT: heparin, haemophilia, VWD, lupus anticoagulant. Isolated prolonged PT: warfarin, vitamin K deficiency, liver disease.
• Exclude platelet clumping before diagnosing thrombocytopenia; schistocytes with low platelets means think TTP.
• ITP: isolated low platelets; treat bleeding or very low counts - steroids, IVIg, then TPO receptor agonists.
• HIT: platelets fall over 50% at 5–10 days with thrombosis - stop all heparin, start a non-heparin anticoagulant, no platelets.
• Haemophilia: X-linked; give factor first, then image; avoid IM injections and NSAIDs.
• VWD is the commonest inherited bleeding disorder - think of it in heavy periods.
• Suspected DVT: Wells score, then ultrasound within 4 hours (or interim DOAC) or D-dimer.
• Apixaban or rivaroxaban first line for VTE; LMWH in pregnancy; warfarin for APS and mechanical valves.
• Provoked VTE: 3 months. Unprovoked: consider long-term if bleeding risk is low.
• Don't screen routinely for cancer or thrombophilia after VTE.
• Calculate creatinine clearance and use the correct DOAC dose - check interactions.
• Warfarin major bleed: PCC plus IV vitamin K. Dabigatran: idarucizumab. Xa inhibitors: PCC, or andexanet for GI bleeds.
• Assess every inpatient for VTE and bleeding risk.

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Guidelines and Further Reading

• NICE NG158: Venous thromboembolic diseases - diagnosis, management and thrombophilia testing (2020, updated)
• NICE NG89: Venous thromboembolism in over 16s - reducing the risk of hospital-acquired DVT or PE
• NICE NG196: Atrial fibrillation (anticoagulation)
• NICE TA697: Andexanet alfa for reversing anticoagulation
• BSH guidelines: ITP; HIT; investigation and management of heritable thrombophilia; antiphospholipid syndrome; warfarin reversal
• International consensus guidelines on ITP (2019)
• UK Haemophilia Centre Doctors' Organisation (UKHCDO) guidance
• RCOG Green-top Guidelines 37a and 37b: VTE in pregnancy
• BNF - for current doses

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