What is the initial approach to managing bleeding disorders?

Initial Approach to Bleeding Disorders

Begin with a structured bleeding history using a validated Bleeding Assessment Tool (ISTH BAT is most common), followed by first-line laboratory testing including CBC with platelet count, PT, aPTT, fibrinogen, and von Willebrand factor studies—this combination identifies the vast majority of clinically significant bleeding disorders. 1, 2

Clinical Assessment

Bleeding History Components

• Family history of bleeding is assessed by 98% of specialists and is critical for identifying hereditary disorders 1, 2
• Medication history including over-the-counter NSAIDs and antiplatelet agents (recorded by 88% of specialists) 1, 2
• Bleeding Assessment Tool (BAT) is used by 80% of specialists, with the ISTH BAT being the preferred instrument (73% usage) 1, 2
• Hypermobility assessment (Beighton score) is performed by 55% of specialists to identify connective tissue disorders like Ehlers-Danlos syndrome 1

Bleeding Pattern Recognition

• Mucocutaneous bleeding (easy bruising, nosebleeds, gum bleeding, heavy menstrual bleeding) suggests platelet or von Willebrand factor disorders 1, 3
• Deep tissue bleeding (muscle hematomas, hemarthroses) indicates coagulation factor deficiencies 3
• Delayed bleeding after initial hemostasis suggests hyperfibrinolysis or factor XIII deficiency 3
• Localized bleeding points toward anatomical causes rather than systemic hemostatic defects 3

Physical Examination Findings

• Ecchymoses, petechiae, or hematomas indicate active or recent bleeding 1
• Jaundice or splenomegaly suggests liver disease as a cause of acquired coagulopathy 1
• Joint and skin laxity raises suspicion for Ehlers-Danlos syndrome 1
• Telangiectasias suggest hereditary hemorrhagic telangiectasia 1

First-Line Laboratory Testing

Universal Initial Tests (Performed by 90-100% of Specialists)

• Activated partial thromboplastin time (aPTT) - performed by 100% of specialists 1, 2
• Prothrombin time (PT) - performed by 100% of specialists 1, 2
• Fibrinogen level (Clauss and/or derived) - performed by 90% in first-line testing 1, 2
• Complete blood count with platelet count - performed by 65% of specialists 1, 2

Von Willebrand Disease Screening (Most Common Bleeding Disorder)

• VWF antigen and VWF activity (ristocetin cofactor or glycoprotein Ib binding) - performed by 84% of specialists as first-line 1, 2
• Factor VIII level - performed by 62% of specialists as first-line (FVIII is carried by VWF) 1, 2
• VWF:Ag to VWF:RCo ratio helps classify VWD subtypes 1

Additional First-Line Tests

• Factor IX and Factor XI assays - performed by 62% of specialists 1, 2
• Iron studies/ferritin - performed by 69% of specialists (iron deficiency is commonly overlooked in bleeding disorders) 1, 2
• ABO blood group - performed by 70% of specialists (Type O blood has 25-30% lower VWF levels) 1, 2
• Thyroid function testing - performed by 45% of specialists 1, 2

Second-Line Testing (When First-Line Tests Are Normal)

Coagulation Factor Assays

• Factor XIII - performed by 60% of specialists as second-line (causes delayed bleeding) 1, 2
• Factors II, V, VII, and X - performed by 52-55% of specialists as second-line 1, 2

Platelet Function Studies

• Platelet function testing (light transmission aggregometry) - performed by 60% of specialists as second-line 1, 2
• Platelet flow cytometry - performed by 42% of specialists as second-line 1, 2
• Platelet function analyzer (PFA-100/200) - performed by 37% of specialists, though conflicting data exist regarding sensitivity and specificity for VWD 1

Specialized Testing

• Fibrinolysis assays - performed by 38% of specialists as second-line 1, 2
• Thrombin generation assay - performed by 28% of specialists as second-line 1, 2
• Genetic testing - performed by 48% of specialists as second-line (best employed in research settings) 1, 2

Interpretation Algorithm

If aPTT is Prolonged and PT is Normal

• Perform 1:1 mixing study to distinguish factor deficiency from inhibitor 1
• If mixing study corrects: Test factors VIII, IX, XI, and XII levels 1
• If mixing study does not correct: Consider lupus anticoagulant or factor VIII inhibitor 1

If PT is Prolonged and aPTT is Normal

• Test factor VII level (extrinsic pathway defect) 1
• Consider liver disease or vitamin K deficiency 1

If Both PT and aPTT are Prolonged

• Test fibrinogen level first 1
• Consider common pathway defects (factors II, V, X) or combined deficiencies 1
• Evaluate for liver disease, vitamin K deficiency, or warfarin effect 1

If Platelet Count is Low

• Examine peripheral blood smear for platelet clumping, large platelets, or schistocytes 3
• Consider VWD Type 2B (causes thrombocytopenia) 1
• Distinguish hypoproliferative from consumptive causes based on mean platelet volume and clinical context 3

If All Initial Tests Are Normal but Bleeding History is Convincing

• Proceed to second-line platelet function testing 1, 2
• Consider rare factor deficiencies (XIII, α2-antiplasmin, PAI-1) 4
• Diagnose as Bleeding Disorder of Unknown Cause (BDUC) if all testing remains normal—this represents 60-70% of patients with mild-moderate bleeding phenotypes 1, 2

Critical Pitfalls to Avoid

• Do not rely on global tests alone (PT/aPTT) as they miss platelet disorders and factor XIII deficiency 5, 4
• Do not use PFA-100/200 as sole screening test for VWD due to conflicting sensitivity/specificity data 1
• Do not dismiss normal laboratory results in patients with convincing bleeding history—consider BDUC and refer to hematology 1, 2
• Delay testing for bleeding disorders until 48-72 hours after blood product transfusions to avoid false results 1
• Recognize that VWF levels vary with stress, inflammation, pregnancy, and estrogen use—repeat testing may be necessary 1
• Do not use group-specific VWF reference ranges based on ABO blood type 2
• Ensure proper sample collection and processing for platelet function tests to minimize preanalytical variability 1, 2

When to Consult Hematology

• Abnormal screening tests suggesting a bleeding disorder 1
• Need for specialized testing (VWF multimer analysis, platelet aggregation studies, genetic testing) 1
• Convincing bleeding history with normal initial testing (possible BDUC) 1, 2
• Perioperative management planning for patients with known or suspected bleeding disorders 1, 6
• Pediatric cases where child abuse must be differentiated from bleeding disorders 1

Registration and Follow-Up

• Register patients with convincing bleeding history even without laboratory abnormalities (75% of specialists do this) 1
• Use standardized terminology: "Bleeding Disorder of Unknown Cause (BDUC)" is preferred over varied terms 1, 2
• Develop individualized treatment plans for perioperative management and bleeding episodes 2, 6