Level 2 of 6Must-remember

Bleeding disorders and anticoagulation reversal

Assess, manage and stay safe — enough on its own

1 / 6

The card — assess, manage, caution

Assessment— look, ask, measure

Ask which drug, and the exact clock time of the last dose: verify against the packet or anticoagulation record, since patients frequently do not know the name of the drug they take — warfarin, unfractionated heparin, low-molecular-weight heparin, fondaparinux, dabigatran, rivaroxaban, apixaban, edoxaban, aspirin, clopidogrel, prasugrel or ticagrelor.
Decide whether this is major haemorrhage: ISTH defines it as fatal bleeding, or symptomatic bleeding into a critical site (intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome), or bleeding causing a fall in haemoglobin of 20 g/L or more, or requiring transfusion of two or more units of red cells — and shock or bleeding that will clearly need products counts as major regardless of numbers.
The site of bleeding names the mechanism: mucocutaneous bleeding (petechiae, easy bruising, gingival bleeding, epistaxis, gastrointestinal or genitourinary bleeding, heavy menstrual loss) means a platelet defect, von Willebrand disease or hereditary haemorrhagic telangiectasia; bleeding into joints, deep muscle and the retroperitoneum means a coagulation factor deficiency or anticoagulant excess; oozing from every venepuncture site, cannula and incision in a shocked, septic patient is DIC until proved otherwise.
Take a structured bleeding history: age at first bleeding, recurrence, number of sites; previous haemostatic challenges (circumcision, dental extraction, tonsillectomy, sports injury, surgery, pregnancy and delivery); menstrual loss heavy enough to cause anaemia; and family history — heritable defects begin in infancy or childhood and involve multiple sites, acquired defects begin later and follow a new drug or disease.
Ask about every drug including over-the-counter and herbal preparations: drugs are the commonest single cause of thrombocytopenia, and high-dose penicillins and vitamin E above 800 mg/day impair platelets.
Look deliberately for wet purpura (blood blisters on the oral mucosa) and retinal haemorrhages — both herald life-threatening haemorrhage in a severely thrombocytopenic patient.
Petechiae are pinpoint, non-blanching haemorrhages appearing first where venous pressure is highest — the ankles and feet in an ambulant patient — and denote a low platelet number rather than dysfunction.
Immediate danger signs: bleeding into the mouth, tongue, floor of mouth or neck, which can obstruct the airway within minutes; any deterioration in conscious level in an anticoagulated patient; shock; wet purpura or retinal haemorrhage in severe thrombocytopenia; a tense, painful limb compartment; and bleeding that continues despite adequate mechanical control.
Know the platelet thresholds: spontaneous bleeding is unusual until the count falls below 10–20 × 10⁹/L, but dysfunctional platelets (uraemia, aspirin, myeloproliferative disease) or a local vascular lesion may bleed heavily at a much higher count.
Send the initial panel before any product is given: full blood count with film, PT/INR, aPTT, fibrinogen, D-dimer, renal and liver function, and group-and-save or crossmatch.
Look at the film before ordering platelets: ask specifically for comment on fragmented red cells (schistocytes) and on platelet clumping — low platelets with schistocytes and a normal PT, aPTT and fibrinogen is a thrombotic microangiopathy, in which platelet transfusion may propagate microthrombi.
A normal PT and aPTT do not exclude a clinically important DOAC level: the time of the last dose and the creatinine are worth more than the coagulation screen, and impaired renal function prolongs the effect of LMWH and every DOAC.Not available at your setup — Renal function (creatinine/urea).
Any anticoagulated patient with head injury, headache, vomiting, confusion or an unexplained fall requires CT of the head even with a normal conscious level — but reversal is not delayed for it when the history and signs are convincing.Not available at your setup — CT scan.
In the elderly, confusion rather than headache may be the only sign of an intracranial bleed, and a normal Glasgow Coma Scale score early after injury does not exclude a haematoma that will expand over hours.
Suspect concealed bleeding when nothing is visible: retroperitoneal and iliopsoas haemorrhage presents with flank or back pain, a femoral neuropathy, or unexplained hypotension with a falling haemoglobin.

Management— do this, in order

Five things proceed in parallel: stop the offending drug; support the circulation while limiting dilution; achieve mechanical control of the bleeding point; give the specific reversal agent and replace what is missing; and treat the underlying cause.
Reversal in a critical-site bleed begins on clinical grounds and is not delayed for laboratory confirmation.
Mechanical control first: firm, uninterrupted direct pressure for a full ten minutes; for epistaxis compress the cartilaginous nose for 10–15 minutes with the patient leaning forward before packing; for a bleeding dental socket, gauze soaked in tranexamic acid held for 20 minutes.
Fluids: warmed crystalloid in 250–500 mL boluses in an adult (10–20 mL/kg in a child), reassessing after each, moving early to blood components rather than chasing a normal blood pressure with clear fluid, which dilutes the remaining clotting factors.
Correct hypothermia, acidosis and hypocalcaemia — each impairs coagulation independently. Minimise venepuncture and avoid non-compressible sites such as the subclavian vein.
Tranexamic acid for most significant bleeding: adults 1 g IV over 10 minutes then 1 g by infusion over 8 hours; children 15 mg/kg IV over 10 minutes (maximum 1 g) then 2 mg/kg/hour; for heavy menstrual bleeding in a known bleeding disorder, 1300 mg orally every 8 hours.
Warfarin with major bleeding: phytomenadione (vitamin K₁) 5–10 mg by slow IV injection PLUS four-factor prothrombin complex concentrate 25–50 units/kg IV; recheck INR at 30 minutes and 6 hours and give further vitamin K until the INR is normal. If PCC is unavailable, fresh frozen plasma 15–30 mL/kg.Doctor / NurseNot available at your setup — Blood & blood products.
Warfarin with minor bleeding: withhold warfarin and give vitamin K 1–3 mg IV. High INR without bleeding: INR below 8 omit doses and recheck daily; INR above 8 (certainly above 10) give vitamin K 1–2.5 mg orally or IV (2.5–5 mg orally is accepted when INR is above 10).Doctor / Nurse
Unfractionated heparin: stop the infusion — the short half-life often suffices; protamine sulfate 1 mg IV per 100 units of UFH given in the preceding 2–3 hours, maximum 50 mg, over at least 10 minutes.Doctor / Nurse
Low-molecular-weight heparin: protamine 1 mg per 1 mg enoxaparin if given within 8 hours, maximum 50 mg — reversal is only partial.Doctor / Nurse
Dabigatran: idarucizumab 5 g IV as two 2.5 g doses; fallback four-factor PCC 25–50 units/kg, and dabigatran is dialysable. Vitamin K is useless.Doctor / NurseNot available at your setup — Dialysis / renal replacement. four-factor PCC 25–50 units/kg
Rivaroxaban, apixaban or edoxaban: andexanet alfa; fallback four-factor PCC 25–50 units/kg, which prospective cohort data suggest restores haemostasis.Doctor / Nurse
Antiplatelet drugs: stop the drug, give desmopressin 0.3 micrograms/kg IV and tranexamic acid; platelets only for life-threatening bleeding or before urgent surgery — the effect persists 7–9 days.Doctor / NurseNot available at your setup — Blood & blood products.
Component targets: platelets above 20 × 10⁹/L in most bleeding patients and above 50 × 10⁹/L for serious bleeding such as intracranial haemorrhage; fibrinogen above 0.8–1.0 g/L with cryoprecipitate or fibrinogen concentrate; fresh frozen plasma only for prolonged PT AND aPTT WITH bleeding, targeting PT and aPTT below 1.5 × normal; red cells for haemoglobin above 80 g/L or symptomatic improvement.Not available at your setup — Blood & blood products.
Correct the fibrinogen with cryoprecipitate BEFORE giving FFP for a prolonged PT and aPTT, then re-test — fibrinogen replacement alone frequently corrects both.Not available at your setup — Blood & blood products.
Paediatric volumes: FFP 15–20 mL/kg, platelets 10–15 mL/kg, cryoprecipitate 5–10 mL/kg, and four-factor PCC 25–50 units/kg as for adults; vitamin K for anticoagulant reversal in a child 250–300 micrograms/kg by slow IV injection, maximum 10 mg.Doctor / Nurse
In known haemophilia give factor concentrate FIRST — before imaging and before the examination is complete; in head injury, factor precedes the CT scan. Factor VIII units = weight (kg) × desired rise in % × 0.5; factor IX units = weight (kg) × desired rise in %.Doctor / NurseNot available at your setup — Blood & blood products.
Vitamin K deficiency: phytomenadione 10 mg IV restores clotting factor levels within 8–10 hours; every neonate should receive phytomenadione 0.5–1 mg intramuscularly at delivery.Doctor / Nurse

Caution— what harms

Never give tranexamic acid in upper urinary tract bleeding (clot may obstruct the ureter) or in DIC (dangerous fibrin deposition may result).
Never order platelets before looking at the film: thrombocytopenia with fragmented red cells and a normal clotting screen is a thrombotic microangiopathy, and platelet transfusion is contraindicated in TTP unless bleeding is life-threatening, because of reports of worsening microangiopathy from propagation of platelet-rich microthrombi.
Never substitute LMWH for heparin in HIT: antibodies cross-react. Stop all forms of heparin including line flushes and heparin-bonded catheters, and start a non-heparin anticoagulant immediately, before confirmatory testing returns.
Never start warfarin alone in HIT: the abrupt fall in protein C may precipitate venous limb gangrene — overlap with the parenteral agent until the INR is 2.0–3.0.
Never correct a number in a patient who is not bleeding: haemostasis in liver disease is rebalanced, not simply impaired, and the INR of a cirrhotic predicts neither bleeding nor its correction.
Never inject protamine rapidly: it causes hypotension, bradycardia and anaphylaxis — give over at least 10 minutes, maximum 50 mg.
Never assume a normal coagulation screen excludes anticoagulation: a normal PT does not exclude a clinically important apixaban or rivaroxaban level; a normal thrombin time effectively excludes dabigatran, but a normal aPTT only makes a significant level unlikely.
Never give high oral doses of vitamin K reflexively: oral doses of 5–10 mg reverse faster but cause days of warfarin resistance; with a mechanical prosthetic heart valve avoid vitamin K if at all possible and use the smallest effective dose, as little as 1 mg orally.
Never give vitamin K prophylactically after superwarfarin rodenticide ingestion — wait for laboratory evidence of anticoagulation; in a child check the INR at 24 and 48 hours and treat only if it rises.Not available at your setup — Coagulation (PT/INR).
Never delay reversal for a CT scan in a convincing critical-site bleed, and never let a normal early GCS reassure you in an anticoagulated head injury — haematoma expansion occurs in the first hours and drives mortality.
Never give routine heparin or antifibrinolytics in DIC: only treatment of the cause alters outcome, and transfusion is given if the patient is bleeding or about to undergo an intervention, never on numbers alone.
Do not forget dilutional coagulopathy: after transfusion of a volume equal to the patient's own blood volume in 24 hours (more than 10 units in an adult) expect thrombocytopenia and prolonged PT and aPTT with hypothermia, citrate-induced hypocalcaemia and hyperkalaemia.
Do not chase a normal blood pressure with clear fluid — it dilutes the remaining clotting factors; move early to components.
Do not miss the pattern that is not bleeding at all: the patient with HIT presents with new thrombosis, and lupus anticoagulant prolongs the aPTT but does not cause bleeding, as does factor XII deficiency.

Refer / escalate

Refer or transfer urgently any critical-site bleed (intracranial, intraspinal, intraocular, retroperitoneal, pericardial, airway or compartment), any bleeding you cannot control mechanically, suspected TTP (microangiopathic haemolytic anaemia with thrombocytopenia and no other explanation — plasma exchange is time-critical and untreated mortality exceeds 95%), suspected HIT, known haemophilia with any head injury, and any patient needing PCC, idarucizumab, andexanet alfa, factor concentrate, plasma exchange or endoscopic, radiological or surgical control that you cannot provide.

The card — assess, manage, caution

Bleeding disorders and anticoagulation reversal — Level 1: CorePrevious Bleeding disorders and anticoagulation reversal — Level 3: Core practiceNext

Read the full lesson free

Create a free account to unlock every page, the level exams, and progress tracking.