Approach to suspected bleeding disorder in adults

Approach to suspected bleeding disorder in adults

1. Core clinical concept (High-yield)

การประเมินผู้ป่วยที่สงสัย bleeding disorder ต้องอาศัย:

Bleeding history (สำคัญที่สุด) + targeted physical exam + screening labs → directed testing

ไม่มี single test ที่คัดกรอง hemostasis ได้ทั้งหมด
และผู้ป่วยจำนวนมากมี bleeding history แต่ lab ปกติ (เช่น VWD, platelet dysfunction, BDUC)

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2. Terminology ที่ต้องแยกให้ชัด (สำคัญทางคลินิก)

Term	ความหมาย	Clinical implication
Petechiae (<2 mm)	capillary bleeding	thrombocytopenia/platelet disorder
Purpura	coalesced petechiae	thrombocytopenia/vasculitis
Ecchymosis (bruise)	subcutaneous bleeding	trauma vs bleeding diathesis
Hematoma	deep tissue bleeding	coagulation factor disorder
Hemarthrosis	joint bleeding	hemophilia / severe factor deficiency
Wet purpura	mucosal hemorrhagic blister	predictor of serious bleeding
Bleeding challenge	surgery, dental extraction, delivery	key diagnostic clue

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3. Primary vs Secondary hemostasis (Clinical pattern recognition)

Primary hemostasis defect (platelet/VWF/vascular)

• Mucocutaneous bleeding
• Epistaxis, gingival bleeding
• Menorrhagia
• Easy bruising
• Immediate bleeding after procedures
  ตัวอย่าง: VWD, platelet dysfunction, ITP

Secondary hemostasis defect (coagulation factors)

• Deep muscle hematoma
• Hemarthrosis
• Delayed bleeding after surgery
  ตัวอย่าง: Hemophilia A/B, factor deficiencies

⚠️ VWD = mixed pattern (primary + secondary)

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4. Initial triage: Active bleeding vs Not actively bleeding

4.1 Actively bleeding patient (suspected undiagnosed bleeding disorder)

ต้องทำพร้อมกัน:

A. หา local cause

• Surgical lesion
• Tumor
• Vascular injury

B. Immediate labs (STAT)

• CBC + platelet count + smear
• PT/INR
• aPTT
• Fibrinogen
• ± D-dimer (ถ้าสงสัย DIC)
• ± VWF / PFA-100 (platelet function analyser) (mucocutaneous bleeding)

C. Empiric hemostatic management (ตามสถานการณ์)

• Platelet transfusion (target ≥50,000; ≥100,000 ถ้า CNS/closed space)
• TXA/EACA (Tranexamic acid/Epsilon-aminocaproic acid) สำหรับ mucosal bleeding
• Cryoprecipitate/fibrinogen concentrate (target fibrinogen >100 mg/dL; >200 mg/dL in pregnancy)
• Vitamin K ถ้าสงสัย deficiency
• PCC / rFVIIa ใน life-threatening bleeding (consult hematology)

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5. Non-bleeding patient: Stepwise diagnostic framework

STEP 1: Confirm “true bleeding disorder” likelihood

เพราะ:

• Bleeding history subjective
• หลายคน bleeding exaggeration แต่ hemostasis ปกติ
• บาง inherited disorders mild → present late

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6. Detailed bleeding history (Most important diagnostic tool)

6.1 Key questions (high-yield checklist)

A. Lifetime bleeding timeline

• Umbilical stump bleeding (Factor XIII)
• Childhood bleeding
• Adult onset (acquired disorder)

B. Bleeding severity markers

• ED visits
• Transfusion
• Surgical intervention
• Iron replacement

C. Bleeding challenge outcomes (very high yield)

ถามเสมอ:

• Surgery
• Dental extraction
• Trauma
• Delivery
• Circumcision (male)

Clinical pearl:

Major procedures without abnormal bleeding = strong evidence against severe inherited bleeding disorder

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6.2 Female-specific history (critical)

• Heavy menstrual bleeding (>8 days, clots >2.5 cm, flooding)
• Iron deficiency anemia
• Postpartum hemorrhage (especially 24–48 hr in VWD)
• Hysterectomy at young age
• Endometriosis / hemorrhagic ovarian cyst (พบร่วม VWD)

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6.3 Associated medical conditions (often overlooked)

• Liver disease
• CKD → uremic platelet dysfunction
• Cancer
• Connective tissue disease (SLE, EDS)
• Hypothyroidism → Acquired VWD
• Alcohol use disorder
• Smoking (associated with ↑ bleeding risk)

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6.4 Medication review (mandatory)

High-yield drugs:

• NSAIDs / Aspirin
• Anticoagulants
• Antiplatelets
• SSRIs
• Glucocorticoids
• Herbal supplements (ginkgo, vitamin E)

Clinical tip:
หยุด OTC/herb ก่อน testing ถ้าเป็นไปได้

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7. Bleeding Assessment Tool (BAT)

เช่น ISTH-BAT
ประโยชน์:

• Low score → strong NPV (rule out bleeding disorder)
• High score → predicts future bleeding risk
• Particularly useful in:
• VWD
• Platelet disorders
• Heavy menstrual bleeding
• BDUC

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8. Targeted physical examination (Diagnostic clues)

8.1 Skin & mucosa

• Petechiae (dependent areas) → thrombocytopenia
• Telangiectasia (lips/fingertips) → HHT
• Perifollicular hemorrhage + corkscrew hair → scurvy
• Periorbital purpura + macroglossia → amyloidosis

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8.2 Systemic findings

Finding	Suggests
Splenomegaly	liver disease, lymphoma
Spider angioma, jaundice	liver disease
Joint hypermobility	Ehlers-Danlos
Harsh systolic murmur	Aortic stenosis → AVWS
Lymphadenopathy	malignancy/infection

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9. Initial laboratory evaluation (All suspected patients)

Core screening panel:

• CBC + platelet count + morphology
• PT/INR
• aPTT
  ± Fibrinogen (if bleeding)

Important:

Normal PT/aPTT does NOT exclude VWD or platelet disorders

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10. Interpretation algorithm (High-yield clinical logic)

10.1 Thrombocytopenia

→ Evaluate causes:

• ITP
• Drugs
• Infection
• Malignancy
• Bone marrow disease

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10.2 PT ↑ + aPTT ↑ (both prolonged)

Suggests:

• Common pathway deficiency (II, V, X, fibrinogen)
• DIC
• Liver disease
• Vitamin K deficiency
• Anticoagulants
• Factor inhibitors
• Amyloidosis (factor X deficiency)

Next step:

• Mixing study
• Fibrinogen
• LFT
• DIC panel

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10.3 PT ↑ only (aPTT normal)

Suggests:

• Factor VII deficiency
• Early vitamin K deficiency
• Warfarin
• Early liver disease
• DIC (early)

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10.4 aPTT ↑ only (PT normal)

Major causes:

• Hemophilia A/B
• Factor XI deficiency
• VWD (severe/type 2N)
• Heparin/DOAC
• Lupus anticoagulant
• Acquired factor VIII inhibitor (acquired hemophilia A)

Next step:

• Mixing study
• Corrects → factor deficiency
• No correction → inhibitor

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10.5 Normal PT + aPTT + platelet count BUT positive bleeding history

Think:

• VWD (most common)
• Platelet function disorder
• Connective tissue disorder
• Vascular purpura
• Hyperfibrinolysis
• BDUC (30–60% in tertiary centers)

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11. VWD testing (must know)

Panel:

• VWF antigen (VWF:Ag)
• VWF activity (VWF:RCo or GPIbM)
• Factor VIII activity
• Multimer analysis (if ratio <0.7)

Key pearls:

• VWF fluctuates with stress, inflammation, estrogen
• Repeat testing often required
• aPTT often normal in mild VWD
• Type 2N VWD → low FVIII mimics hemophilia A

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12. Platelet function testing (when indicated)

Methods:

• Platelet aggregometry (gold standard)
• PFA-100 (adjunct)
• Genetic testing (selected cases)
• Electron microscopy (storage pool disorders)

Limitations:

• Operator dependent
• Poor standardization
• No single comprehensive test

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13. Special entities to always consider

• Acquired hemophilia A (new severe bleeding + prolonged aPTT)
• Acquired VWD (AS, malignancy, hypothyroidism)
• Amyloidosis (factor X deficiency, periorbital purpura)
• Hyperfibrinolysis (delayed bleeding)
• Factor XIII deficiency (normal PT/aPTT + delayed bleeding + poor wound healing)

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14. When to refer to hematologist (Guideline-based)

• Active bleeding requiring hemostatic products
• Unexplained abnormal PT/aPTT/CBC
• Strong bleeding history with normal labs
• Suspected VWD, platelet disorder, ITP
• Preoperative bleeding risk concern
• Family history of bleeding disorder
• Possible acquired inhibitor

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15. Key clinical pearls (Exam + Real practice)

• Bleeding history > lab screening in diagnostic value
• Normal surgery/dental extraction = strong negative predictor of inherited bleeding disorder
• Mucocutaneous bleeding → platelet/VWD
• Deep hematoma/hemarthrosis → coagulation factor defect
• Normal PT/aPTT does NOT exclude VWD
• Mixing study = key test to differentiate inhibitor vs deficiency
• Up to 60% of patients with bleeding symptoms have normal lab (BDUC)
• New severe bleeding in older adult → think acquired inhibitor first

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