Coagulopathy

The Bleeding patient

• Not all trauma patients require coagulation testing
• Indicated if spontaneous bleeding, multiple untraumatised bleeding sites, delayed bleeding several hours after trauma and bleeding into deep tissues or joints
• History: Previous episodes of abnormal bleeding in patient or family members, excessive bleeding after dental extractions/surgery/trauma, liver disease and drugs
  • Ethanol, aspirin, NSAID’s, anticoagulants, antibiotics and OTC (garlic, ginseng, ginkgo biloba, vitamin E)
• Platelet deficiency: Bleeding into mucocutaneous surfaces, petechiae, ecchymoses, epistaxis, GI/GU bleeding or heavy menstrual bleeding and purpura
• Coagulation deficiency: Bleeding into joints, fascial planes, retroperitoneum and delayed bleeding
• DIC: Both mucocutaneous and joints/potential spaces

Normal haemostasis

• Primary haemostasis = Platelet plug
  • Need normal vascular subendothelium (collagen), functional platelets, normal vWF (connects platelet to endothelium via glycoprotein Ib) and normal fibrinogen (connects platelets to each other via glycoprotein IIb/IIIa)
• Secondary haemostasis = Cross-linked fibrin clot
  • Two pathways with common pathway from activation of Factor X
  • Factor Xa, Factor Va, phospholipid and calcium = Thrombinase complex that more efficiently converts prothrombin to thrombin than free Factor Xa
• Fibrinolytic system

The coagulation pathway

APTT = Table Tennis = Intrinsic

 – TwelvE

 – EleveN

 – NinE

 – EighT

 – TeN

 – Prothrombin to Thrombin

 – Fibrinogen to Fibrin

 – XIII cross-linking

PT = Tennis = Extrinsic

 – Factor VII

 – Factor X

 – Prothrombin to Thrombin (II)

 – Fibrinogen to Fibrin

 – XIII cross-linking

 – IX in there somewhere (TV)

The fibrinolytic pathway

Tissue plasminogen activator (tPA) released from endothelial cells and

Converts plasminogen synthesised in the liver and adsorbed into fibrin clots

Into plasmin

Plasmin degrades fibrinogen and fibrin monomer into 

fibrin degradation products

Plasmin degrades cross-linked fibrin into D-dimer

Antithrombin forms complexes with all serine protease coagulation factors

(Factors XIIa, XIa, IXa and thrombin) to inhibit their function

 – Heparin potentiates this function

Activated Protein C binds to cell-surface-bound Protein S, which together

Inactivate Factors Va and VIIIa

Factor V Leiden mutation prevents activated Protein C from binding and

Inhibiting Factor Va resulting in prolonged thrombogenic activity of Factor Va

Thrombophilias

• Acquired – Arterial and/or venous clots
  • Essential thrombocythaemia
  • Polycythaemia vera
  • Paroxysmal nocturnal haemoglobinuria
  • Antiphospholipid syndrome
  • Cancer (often occult at time of thrombosis)
• Inherited (venous clots)
  • Factor V Leiden
  • Prothrombin mutations
  • Protein C and S deficiency
  • Hyperhomocysteinaemia
  • Antithrombin III deficiency

Tests of haemostasis

• Primary haemostasis
  • Platelet count
  • Bleeding time: Prolonged in thrombocytopaenia or abnormal Plt function (vW disease, antiplatelet drugs, uraemia, liver disesase)
• Secondary haemostasis
  • Prothrombin time (11-13s; INR 1.0)
    • Extrinsic and common pathways (Factors II, VII, X, fibrinogen)
    • Prolonged in warfarin, liver disease and antibiotics that inhibit vitamin K-dependent factors (cefotaxime)
  • Activated partial thromboplastin time (APTT) (22-34s) Activated by kaolin
    • Intrinsic and common (XII, IX, IX, VIII, X, II and fibrinogen)
    • Prolonged in heparin therapy and factor deficiencies (need to be <30% of normal)

Tests of haemostasis

• Fibrinogen level (2-4g/L)
  • Low in DIC
  • Elevated in inflammatory processes
• Thrombin clotting time (TCT)
  • Conversion of fibrinogen to fibrin
  • Prolonged in low fibrinogen level, abnormal fibrinogen molecule (liver disease), heparin, fibrin degradation products, paraprotein (e.g. multiple myeloma) and sometimes hyperfibrinogenaemia
• Fibrin degradation products and D-dimer
  • FDP tests for breakdown products of fibrinogen and fibrin monomers
  • D-dimer tests for breakdown of cross-linked fibrin

Tests of haemostasis

• Antiphospholipid antibodies
  • Lupus anticoagulant elevated in SLE and other autoimmune conditions
  • Anticardiolipin antibodies – Elevated in SLE, other autoimmune conditions, Syphilis and Behcet’s disease
  • Increased risk of spontaneous abortions, fetal growth retardation
• Anti-Factor Xa activity
  • Used to monitor LMWH

ROTEM

• EXTEM
  • Extrinsic pathway testing (not affected by heparin)
  • Coagulation activated by tissue factor 
• FIBTEM
  • EXTEM with addition of platelet inhibitor. Comparison with EXTEM identifies effect of fibrinogen concentration and function
• APTEM
  • EXTEM with addition of aprotinin (to inhibit fibrinolysis). Comparison with EXTEM identifies hyperfibrinolysis
• INTEM
  • Intrinsic pathway and heparin sensitive
• HEPTEM
  • INTEM with addition of heparinase. Comparison to INTEM identifies heparin effect

ROTEM

• Targets
  • FIBTEM A5 >10mm
  • EXTEM CT < 80s
  • EXTEM A10 >40mm
• Indications
  • Haemodynamic instability from suspected or proven haemorrhage
• Normal values of EXTEM
  • Clotting time (CT) <80s (time to initiation of clotting)
  • Clot formation time (CFT) <160s (time to clot firmness of 20mm)
  • Amplitude at 5 min (A5) >35mm
  • Amplitude at 10 min (A10) > 45mm
  • Maximum clot firmness (MCF) 50-72mm
  • Maximum lysis (ML) <15% (% of MCF)

ROTEM

• Limitations
  • Platelet inhibitors
    • No detection of antiplatelet effects
    • No detection of von Willebrand syndrome
    • No detection of functional platelet impairment in renal failure
  • Anticoagulants
    • Poor sensitivity to LMWH
    • Poor sensitivity to oral anticoagulants

ROTEM

• Hyperfibrinolysis = ML % > 15% = TXA 1g
• Hyperfibrinolysis + low fibrinogen = 
  • FIBTEM cT >600s AND EXTEM A5 < 35mm = 
  • TXA 1g + Fibrinogen concentrate 4g (one off) OR CRYO 20U
• Low fibrinogen
  • FIBTEM A5 <8mm = Fibrinogen concentrate 4g one off or Cryo 20U
  • FIBTEM A5 8-10mm = Cryo 10U
• Low platelets
  • EXTEM A5 <35mm & FIBTEM A5 >10mm = 1 dose of platelets
• Factor deficiency
  • EXTEM-CT >90s & EXTEM A5 <35mm = 2-4U FFP

Acquired platelet disorders

• Risk of spontaneous bleeding (including ICH) concerning below 10-20 (higher if liver, renal, antiplatelets, connective tissue disease, peptic ulcer disease, hypertension, elderly, falls risk and lifestyle activities)
• Disease process causing thrombocytopaenia also alters bleeding risk e.g. ITP (normal high functioning platelets <10 less bleeding risk than aplastic anaemia with dysfunctional platelets <50
• Decreased platelet production
  • Marrow infiltration (tumor, infection), viral infection (rubella, HIV), drugs, radiation, B12/folate deficiency
• Increased platelet destruction
  • ITP,  TTP, HUS, DIC, viral (HIV, mumps, varicella, EBV), drugs (heparin, protamine), HELLP, pre-eclampsia, gestational thrombocytopaenia
• Platelet loss
  • Excessive haemorrhage, haemodialysis, ECMO/CPB
• Splenic sequestration
  • Sickle cell disease, cirrhosis

Acquired platelet disorders

• Drugs
  • Produce thrombocytopaenia
    • Heparin 4+
    • Gold salts 4+
    • Sulfa antibiotics 4+
    • Quinine 4+
    • Ethanol (chronic) 4+
    • Aspirin 3+
    • Rifampicin 2+
    • Abciximab and eptifibatide 2+
    • Thiazides and frusemide 2+
    • Acyclovir 2+
    • Procainamide 2+
    • Digoxin 2+
    • Cimetidine and ranitidine 2+
    • Phenytoin and valproate 1+
    • Penicillins and cephalosporins 1+

Acquired platelet disorders

• Drugs
  • Impair platelet function
    • Aspirin
    • NSAID’s
    • GpIIb/IIIa inhibitors: Ticlopidine
    • ADP inhibitors: clopidogrel, ticagrelor
    • Penicillins and cephalosporins
    • CCB
    • Propranolol
    • GTN
    • Antihistamines
    • Phenothiazines
    • Cyclic antidepressants

Reduced platelet production

• Neonatal: Congenital infections e.g. CMV, rubella
• Older children:  Aplastic anaemia, marrow infiltration by leukaemia/lymphoma or myelofibrosis

Increased platelet destruction

• Idiopathic thrombocytopaenic purpura
  • Acquired autoimmune condition resulting in rapid destruction of platelets
  • Thrombocytopaenia, purpura or petechiae, normal bone marrow and no other identifiable cause
  • Anti-platelet antibodies cover platelets, which are then removed by reticuloendothelial system
  • In some cases, same antibody will bind to megakaryocytes in marrow, limiting the bone marrow response
  • Circulating platelets still function normally despite antibodies reducing the actual bleeding risk
  • Presence of lymphadenopathy, hepatosplenomegaly, pallor or hyperbilirubinaemia suggests alternative diagnosis such as leukaemia, lymphoma, SLE, infectious mononucleosis or haemolytic anaemia
  • FBC should be normal aside from low platelets with smear showing low number but normal platelets

Increased platelet destruction

• ITP continued…
  • Acute ITP
    • More common in younger children, M=F and resolves over 1-2 months
  • Chronic ITP
    • Lasts >3 months, more common in adults and females, rarely remits without treatment
    • More likely to have underlying autoimmune disorder, HIV, SLE, Graves, Hashimoto’s or antiphospholipid antibody syndrome

Increased platelet destruction

• ITP Treatment
  • All patients should have bleeding risk minimised (avoid antiplatelets/anticoagulants, unnecessary procedures, trauma, good blood pressure control, treatment of hepatic/renal disease, reduce falls risk
  • Children with platelets > 20 and no bleeding do not need hospitalisation or treatment
  • Children with platelets <20 and significant bleeding or <10 with no or minimal bleeding should receive IVIG or corticosteroids
  • Adults with platelets >30 do not need treatment
  • 20 – 30 consider steroids
  • <20 or significant mucocutaneous bleeding: Hospitalisation + Steroids
  • >20 if only minor petechiae: Outpatient therapy
  • Corticosteroid therapy: 2-4mg/kg/day (60-100mg daily PO) with taper once platelet count risen to normal
  • IVIG 1g/kg/day for 2 days or anti-D for very low platelet counts and bleeding
  • Platelet transfusions only if life-threatening bleeding and after first dose of steroid/IVIG

Platelet dysfunction

• Uraemia
• Liver disease
• DIC
• Antiplatelet antibodies (SLE)
• Cardiopulmonary bypass
• Myeloproliferative disorders (polycythaemia vera, thrombocytosis, chronic myeloid leukaemia, acute lymphocytic or myelogenous leukaemia)
  • Platelets often dysfunctional despite normal number
  • Transfuse platelets to above 50 if bleeding

Platelet dysfunction

• Dysproteinaemias (multiple myeloma, Waldenstrom’s macroglobulinaemia)
  • Plasmapheresis may reduce protein interference with platelet function
• Von Willebrand disease (congenital or acquired)
• Drugs
  • Aspirin (onset 1 hour; duration 7 days)
  • Most NSAID’s (onset 1 hour; duration 1 day)
  • Piroxicam (onset 1 hour; duration 2 days)
  • Ticagrelor/clopidogrel (onset 1-2 days; duration 4-7 days)

Acquired coagulation disorders

• Liver disease
  • Hepatocytes synthesise all coagulation factors (except Factor VIII – hepatic sinusoidal cells + endothelial cells) so get deficiency in all (including Protein C and S)
    • Vitamin K is fat soluble so get impaired synthesis of Vit-K-dependent factors with impaired bile acid metabolism (e.g. PBC), intrahepatic or extrahepatic cholestasis and bile acid binding medications
  • Thrombocytopaenia in hepatic disease is most often due to portal hypertension and subsequent congestive hypersplenism + splenic sequestration
  • Increased fibrinolysis due to reduced synthesis of alpha-2 plasmin inhibitor resulting in low fibrinogen levels, mild elevation of FDP and D-dimer
  • Abnormal fibrinogen molecules can be synthesised and converted to fibrin molecules that do not polymerise normally
  • Distinguishing DIC from hepatic coagulopathy can be difficult as both get decreased platelets, decreased coagulation factors and hypofibrinogenaemia, however, D-dimer should be normally or only mildly elevated in isolated liver disease
  • Only needs treatment if clinically significant bleeding or procedure/surgery
    • PO or IV vitamin K to all bleeding patients with hepatic coagulopathy
    • FFP can temporarily replace coagulation factors (although volume required can limit use)
    • Cryoprecipitate if active bleeding and fibrinogen <1.0
    • Platelet transfusion if <100 and active bleeding (as high risk factors exist)
    • Desmopressin lacks conclusive evidence but side effects appear to be minimal (0.3mg/kg IV BD up to 3 doses)

Acquired coagulation disorders

• Renal disease
  • Abnormal clotting factors, dialysis-induced thrombocytopaenia and uraemia-induced platelet dysfunction
  • Prevention through ensuring adequate nutrition, folate/B12/iron supplementation, optimising dialysis and correction of anaemia with erythropoietin
  • Acute bleeding can be treated with dialysis (improves platelet function for 1-2 days), desmopressin, conjugated oestrogens, cryoprecipitate and platelet transfusion (rarely helpful as rapidly acquire uraemic defect in fx)

Acquired coagulation disorders

• DIC
  • Inappropriate and widespread activation of coagulation system with intravascular fibrin formation
  • Concomitant activation of fibrinolytic system results in breakdown of fibrin clots, consumption of coagulation factors and bleeding
  • Common pathway is activation of cytokines and tissue factor with extrinsic coagulation cascade upregulation
  • Clinical features
    • Bleeding, thrombosis, purpura fulminans and MODS
    • Most common manifestation is bleeding > thrombosis
  • Lab findings
    • Prolonged PT, low platelet count and low fibrinogen level
    • Thrombocytopaenia is most common finding (progressive drop is sensitive but not specific)
    • Fibrinogen can remain normal as is an acute phase reactant
    • D-dimer may be slightly more specific for DIC than increased FDP
    • Evidence of haemolysis may be evident (raised LDH, reduced serum haptoglobin, schistocytes, free Hb)
    • Chronic DIC shows minor abnormalities reflecting hepatic/bone marrow compensation for consumption

Acquired coagulation disorders

• DIC scoring system
  • Platelet count
    • 0 if >100, 1 if 50-100 and 2 if <50
  • Elevated FDP or D-dimer
    • 0 if no increase, 2 if moderate, 3 if large increase
  • Prolonged PT
    • O if <3s prolongation, 1 if 3-6s prolongation, 2 if >6s prolongation
  • Fibrinogen level
    • 0 if >1.0, 1 if <1.0
  • If 5 or greater = DIC
  • If 4 or less = No overt DIC. Repeat in 1-2 days

Acquired coagulation disorders

• Common causes
  • Infection: Most common. 10-20% of Gram negative sepsis patients suffer DIC. More likely in asplenic and cirrhotic patients. Septic patients suffer bleeding > thrombosis
  • Carcinoma: Most adenocarcinomas show thrombosis (Troussaeu syndrome) except prostate cancer causes bleeding. Often chronic DIC with compensation of coagulation factors by bone marrow
  • Acute leukaemia: Blast cells release procoagulant enzymes, especially at time of chemotherapy. More bleeding > thrombosis
  • Trauma: Especially brain injury, crush injury, burns, hypo/hyperthermia, rhabdo, fat embolism and hypoxia
  • Acute hepatic failure and pancreatitis
  • Pregnancy: Placental abruption, amniotic fluid embolus, septic abortion, HELLP
  • Vascular disease: Large aortic aneurysms, vasculitis
  • Envenomation
  • ARDS: 20% of ARDS patients develop DIC and 20% of DIC patients develop ARDS
  • Transfusion reactions: Acute haemolytic reaction

Acquired coagulation disorders

• DDx of DIC
  • Primary fibrinolysis (plasmin and fibrinolysis activation without thrombin)
  • Severe liver disease
  • D-dimer allows differentiation as should be normal or mildly elevated in above

Acquired coagulation disorders

• Treatment of DIC
  • Rests on supportive measures and management of underlying illness
  • Replacement of platelets, coagulation factors and fibrinogen should only occur if documented DIC with active bleeding or impending invasive procedure
  • Goal is to raise fibrinogen to 1.0-1.5 with cryoprecipitate or fibrinogen concentrate
  • Platelet replacement considered if <50 and bleeding or <10-20 without bleeding
  • FFP to replace clotting factors if bleeding
  • Give Vitamin K and folate to all DIC patients
  • Heparin
    • Unclear role but usually given for those with thrombotic complications of acute DIC (e.g. purpura fulminans) or chronic DIC with thrombosis
    • LMWH = UFH
  • Antifibrinolytic agents (e.g. e-aminocaproic acid and TXA) are used with great caution and often in conjunction with heparin if at all

Acute vs. chronic DIC

• Both represent imbalance of coagulation factor and platelet production and consumption
• Acute (decompensated) far more likely to present with bleeding vs. chronic
• Chronic (compensated) more likely to present with thrombosis as procoagulant factors keep pace with ongoing generation of thrombi
• Acute
  • Recent critical illness
  • Bleeding
  • Thrombocytopaenia
  • Prolonged PT and APTT
  • Low plasma fibrinogen
  • Elevated D-Dimer
  • Microangiopathic changes on film

Acute vs chronic DIC

• Chronic
  • Cancer
  • Thromboembolism
  • Mild or no thrombocytopaenia
  • Normal or mildly raised PT/APTT
  • Normal or slightly elevated fibrinogen
  • Raised D-dimer
  • Microangiopathic changes
  • Libman-Sacks endocarditis
  • Troussea’s syndrome (migratory superficial thrombophlebitis)
• Exception to this is acute promyelocytic leukaemia that presents with acute DIC

Circulating Inhibitors of coagulation

• Aka circulating anticoagulants = Antibodies against coagulation factors
• May develop spontaneously but mostly seen in those with reception of plasma products e.g. haemophilia
• Two most common are Factor VIII inhibitors and antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies – both non-specific)
• Factor VIII inhibitors
  • Mostly seen in patients Haemophilia A
  • If spontaneously arising (1.4 cases per million) mortality = 22%
    • Usually in elderly patients with SLE, RA, ulcerative colitis, multiple myeloma, Waldenstrom’s macroglobulinaemia, MGUS or those with allergies to penicillin, sulfonamides and phenytoin
  • Classic lab studies show normal PT, normal TCT and massively prolonged APTT that does not correct with ‘mixing’ (that is, mixing with normal plasma and thus replacing Factor VIII deficiency)
  • Factor VIII-specific assay will show very low or absent activity
  • Quantitative measurement of inhibitor via Bethesda Inhibitor Assay is important for emergency management
  • Long-term management is steroids, IVIG, cytotoxic agents or rituximab
  • In acute episodes, consult haematology but treatment will include Factor VIII, Factor IX complex, purified prothrombin complex, recombinant Factor VIIa, desmopressin and plasmapheresis + Conservative compression and immobilisation of bleeding site

haemophilias

• Haemophilia A (Factor VIII), Haemophilia B (Factor IX – Christmas disease)
  • Indistinguishable on coag testing
  • Both have prolonged APTT with normal PT
• VonWillebrand Disease is hereditary deficiency of vWF
• Usually present in childhood but mild forms may not present until adulthood
• Suspect in any patient with excessive bleeding after minor trauma, minor surgery, spontaneous bleeding (esp. joints/muscles) or multiple areas
• May present with delayed bleeding following trauma, presumably due to instability of initial platelet plug that lacks fibrin clot formation
• Consider if raised APTT of unclear aetiology
• Those with vWD may present with both platelet and clotting factor problem presentations

Haemophilias

• Haemophilia A (1/10 000) vs. Haemophilia B (1/25000-35000) = Together make up 99%
• Both X-linked disorders thus women tend to be asymptomatic carriers
• 1/3 of new cases of Haemophilia A are due to spontaneous mutations and lack family history and 1/5 of new Haemophilia B cases
• Factor levels <1% = Severe (spontaneous bleeding)
• Factor levels 1-5% = Moderate (usually traumatic vs. spontaneous bleeding)
• Factor levels 5-40% = Mild disease (bleed only after trauma)
• Unless there is another disorder, haemophilia patients do not have trouble with minor abrasions or cuts
• For serious unexplained haemorrhage, send labs and use FFP while awaiting results
• Diagnosis
  • PT normal
  • APTT significantly abnormal unless activity >30-40%
  • Bleeding time in both is normal and not helpful
  • Specific factor assays can confirm diagnosis
  • If mild-moderate bleeding episode and known haemophiila, coagulation studies are not generally helpful

haemophilias

• Treatment
  • Early and complete factor replacement at the same time as other resuscitative and diagnostic techniques
  • Any new headache, focal neurology, ALOC or blunt head injury warrants non-con CT to rule out ICH (most common cause of death in haemophilia)
  • If focal neurology localises to spinal cord – need urgent MRI for epidural haematoma
  • Back, thigh, groin or abdominal pain may have retroperitoneal bleed and need non-contrast CT (esp. iliopsoas bleeds)
    • Iliopsoas bleed can also compress femoral nerve with resultant symptoms
  • Consider compartment syndrome after muscle bleeds but only measure pressures after factor replacement
  • Haemarthrosis is one of the most common manifestations of haemophilia and patients can reliably report when bleeding is occurring (even if no clinical evidence of this)
    • Prompt treatment can prevent and reduce long-term haemophilic arthropathy
    • May present as irritable infant with no clinical findings
  • Treat pain aggressively
  • Do not insert any central lines, ABG, IM injections or lumbar punctures without factor coverage
  • Consult haematology early

haemophilias

• Factor replacement therapy
  • Recombinant Factor VIII or IX
  • Dosing is based on:
    • Clotting factor volume of distribution
    • Half-life of factor: Factor VIII (8-12 hours), Factor IX (16-24 hours)
    • Haemostatic level of factor required to control bleeding (see next table)
  • Clotting factor is dosed in units of activity
  • One unit of factor = amount of factor present in 1mL of normal plasma

haemophilia

haemophilia

• Mild haemophilia A
  • May not require factor replacement and can receive desmopressin instead
  • Desmopressin causes release of vWF from endothelial stores, which can carry additional Factor VIII
  • 0.3mcg/kg IV over 15-30 minutes BD for three doses
  • Intranasal option also available
  • Increases Factor VIII level by 2-3 times normal
  • Antidiuretic agent so may require fluid restriction during therapy

haemophilia

• Haematuria
  • Common but usually not severe
• Inhibitors
  • Mostly in severe haemophilia and can lead to failure of Factor replacement to stem bleeding AND anaphylaxis with factor replacement in Haemophilia B
  • Seen in 10-25% of Haemophilia A patients and 1-2% of Haemophilia B
  • Factor replacement is guided by quantitative (Bethesda) inhibitor assay (always ask if known inhibitors)
  • Consult haematology immediately
• Not all patients will require admission. Gauged on site of bleeding, analgesia requirements, ongoing factor replacement needs and ability to self-care

Von willebrand disease

• Most common congenital bleeding disorder
• 1% of population
• vWF is a glycoprotein synthesised stored and secreted by vascular endothelial cells (NOT THE LIVER)
  • Cofactor for platelet adhesion
    • When exposed to subendothelial matrix, vWF undergoes structural change allowing it to bind to platelet glycoprotein Ib, leading to platelet activation and adhesion to other platelets and damaged endothelium
  • Carrier protein for Factor VIII
    • Protects Factor VIII from proteolytic degradation within plasma so in deficiency get shortened half-life of Factor VIII presenting as Haemophilia A-type syndrome
• Type 1: Partial quantitative disease
• Type 2: Qualitative
• Type 3: Severe and complete deficiency (autosomal recessive)

Von willebrand disease

• Clinical presentation
  • Skin and mucosal bleeding including recurrent epistaxis, unusual bleeding, gingival bleeding, GI bleeding, menorrhagia
  • Haemarthrosis rare unless severe disease
  • Mild cases may only present after surgery/procedure/anticoagulant/antiplatelets
• Diagnosis
  • Typically prolonged bleeding time, low or normal vWF antigen, low vWF activity
  • PT should be normal and 50% of patients have mildly prolonged APTT
  • Blood type O have 30% lower vWF levels normally

Von Willebrand disease

• Treatment
  • Avoid antiplatelet/anticoagulants
  • Desmopressin therapy for acute bleeding or prophylaxis in mild disease
  • Cryoprecipitate for bleeding episodes in moderate-severe disease or not responding to desmopressin
  • Platelet transfusions can be beneficial in type 3 disease that does not respond to cryo
  • Oral contraceptives can raise vWF levels and limit menorrhagia in young women
  • Antifibrinolytic mouthwash therapy for oral/dental bleeding

Last Updated on October 2, 2020 by Andrew Crofton