Bleeding Disorder of Unknown Cause (BDUC)
1. Definition (Key concept)
BDUC (Bleeding Disorder of Unknown Cause) =
ภาวะเลือดออกผิดปกติทางคลินิก +
ผลตรวจ hemostasis มาตรฐาน “ปกติทั้งหมด”
→ หลัง exclusion
ของ known bleeding disorders
เป็น diagnosis of exclusion เท่านั้น
ต้องมี:
- Documented
bleeding phenotype (เช่น BAT positive)
- Normal
comprehensive hemostatic testing
2. Diagnostic Criteria (Practical checklist)
วินิจฉัย BDUC เมื่อมี:
2.1 Clinical bleeding history +
2.2 Normal laboratory evaluation ครบ:
- CBC +
platelet count & morphology
- PT /
aPTT / thrombin time / fibrinogen
- VWF
antigen + activity (VWD panel)
- Factor
VIII, IX, XI activity
- Platelet
aggregation (gold standard)
⚠️ ไม่มี bleeding
history → ไม่เรียก
BDUC แม้ lab ผิดปกติ
3. Epidemiology (High-yield)
- พบใน 46–66% ของผู้ป่วยที่ส่ง consult
bleeding tendency
- Female
predominance: 66–87%
- อายุเฉลี่ยวินิจฉัย: 33–42 ปี
- ~50% มี family history (มัก autosomal
dominant pattern)
Clinical implication:
ผู้หญิงที่มี heavy menstrual bleeding +
lab ปกติ = ต้องคิดถึง BDUC สูง
4. Pathophysiology (Current understanding)
ยังไม่ทราบสาเหตุชัดเจน
คาดว่าเป็น:
- Polygenic
low-penetrance variants
- Mild
platelet/vascular dysfunction ที่ตรวจไม่พบ
- Undiscovered
hemostatic disorders
- Connective
tissue fragility
5. Clinical Features (Pattern recognition)
5.1 Most common manifestations
เรียงจากพบบ่อย:
1.
Heavy menstrual bleeding (HMB) — สูงสุด
(~90%)
2.
Mucocutaneous bleeding
o Epistaxis
o Gingival
bleeding
o Easy
bruising
3.
Excessive surgical bleeding
4.
Postpartum hemorrhage (PPH)
Severity:
- Comparable
กับ mild VWD
- 23% เคยต้อง transfusion (บาง cohort)
5.2 Associated complications
- Iron
deficiency (very common)
- Iron
deficiency anemia
- Fatigue,
RLS, hair loss, mood change
Clinical pearl:
Iron deficiency + unexplained bleeding = red flag ของ BDUC
6. Evaluation Framework (Stepwise approach for
physicians)
STEP 1: Confirm “true abnormal bleeding”
ใช้:
ISTH-BAT (recommended)
Cut-off:
|
Group |
Positive BAT |
|
Child |
≥3 |
|
Adult male |
≥4 |
|
Adult female |
≥5–6 (age dependent) |
ข้อควรจำ:
- BAT มี high NPV
- Young
patients อาจ BAT ต่ำเพราะไม่มี bleeding
challenge
STEP 2: Detailed history (Critical)
ต้องถาม:
A. Bleeding challenges (high yield)
- Surgery
- Dental
extraction
- Delivery
- Trauma
B. Menstrual history (สำคัญที่สุด)
- Duration
>7 days
- Clots
>2.5 cm
- Flooding
- Iron
therapy need
- PPH
history
C. Family history
- Bleeding
- Iron
deficiency anemia
D. Medication review
- NSAIDs
- SSRIs
- Antiplatelets
- Herbal
supplements (ginkgo, vitamin E)
STEP 3: Exclude acquired causes ก่อน
ภาวะที่ mimic BDUC:
- CKD
(uremic platelet dysfunction)
- Liver
disease
- Myeloproliferative
neoplasm
- Hypothyroidism
- Alcohol
use disorder
Clinical tip:
Treat underlying disease ก่อน extensive
hematologic workup
7. Laboratory Evaluation to exclude specific disorders
7.1 Initial testing (all patients)
- CBC +
smear
- PT /
aPTT
- Fibrinogen
- VWD
panel (VWF:Ag + activity)
- Factor
VIII, IX, XI
- Platelet
aggregation (if screening negative)
7.2 Additional testing (Selected cases)
Vitamin C level (often overlooked)
ควรพิจารณาใน:
- Easy
bruising
- Hematoma
- Malnutrition
/ restrictive diet
- Post-bariatric
surgery
Cutoff: <0.2 mg/dL →
scurvy
รักษาง่ายและ low risk
Factor XIII (important pitfall)
สงสัยเมื่อ:
- Delayed
bleeding
- Normal
PT/aPTT
- Poor
wound healing
- Umbilical
stump bleeding (history)
Hyperfibrinolysis testing
คิดถึงเมื่อ:
- Delayed
post-op bleeding
- Normal
routine labs
- Severe
unexplained bleeding
Tests:
- D-dimer
- ECLT
(Euglobulin clot lysis time)
- Fibrinogen
trends
Chromogenic FVIII assay
สำคัญใน:
- Suspected
mild hemophilia A
- Female
carriers
- Normal
one-stage FVIII แต่ bleeding phenotype
8. Differential Diagnosis (Must exclude before BDUC)
|
Condition |
Key distinguishing feature |
|
VWD |
↓
VWF activity |
|
Platelet function disorder |
Abnormal aggregometry |
|
Mild hemophilia |
↓
factor activity |
|
Ehlers-Danlos syndrome |
Hypermobile joints, skin
fragility |
|
HHT |
Telangiectasia + AVM |
|
Scurvy |
Low vitamin C |
|
Rare factor deficiency (XIII) |
Normal PT/aPTT |
9. Diagnosis Summary (Clinical definition)
วินิจฉัย BDUC เมื่อ:
1.
Positive bleeding phenotype (BAT + history)
2.
Normal:
o CBC/platelets
o PT/aPTT/fibrinogen
o VWD
testing
o Factor
VIII/IX/XI
o Platelet
function testing
3.
Excluded secondary causes
4.
No identifiable specific disorder
10. Management Principles (Evidence-limited but
practical)
10.1 General bleeding risk reduction
- Avoid
NSAIDs/antiplatelets (ถ้าไม่จำเป็น)
- Limit
alcohol
- Trauma
prevention
- Medical
alert documentation
- Pre-procedure
communication (critical)
10.2 Iron deficiency surveillance (standard care)
Recommended:
- CBC +
ferritin annually (especially menstruating patients)
- Treat
early iron deficiency
- IV
iron if severe blood loss
11. Perioperative Management (High clinical relevance)
General strategy:
- Consult
hematology/hemostasis expert
- Avoid
neuraxial anesthesia (if possible)
- Multidisciplinary
planning (surgeon + anesthesia)
Pharmacologic prophylaxis:
1.
Tranexamic acid (TXA) – first-line
2.
± Desmopressin (DDAVP)
3.
Platelet transfusion (severe cases)
Combination therapy often used in high-risk surgery
⚠️ No reliable lab marker to
monitor response
12. Heavy Menstrual Bleeding (Most common scenario)
ต้อง exclude structural causes
(PALM-COEIN) ก่อน
Treatment options:
- TXA
(intermittent during menses)
- DDAVP
during menses
- Hormonal
therapy (OCP, LNG-IUS)
- Combination
therapy if refractory
- Endometrial
ablation / hysterectomy (selected, no fertility plan)
13. Pregnancy & Delivery (Important for OB/ER)
Risk: ↑
Postpartum hemorrhage (PPH)
Management:
- Avoid
forceps/instrumental delivery if possible
- TXA
during labor (e.g., 1 g IV/PO)
- Close
PPH monitoring
- Platelet
transfusion / fibrinogen correction if bleeding
- Vaginal
delivery preferred unless obstetric indication for C/S
TXA appears safe (extrapolated WOMAN trial data)
14. When to Refer Hemostasis Specialist
- Unexplained
excessive bleeding
- Planned
major surgery
- Pregnancy
with bleeding history
- Recurrent
transfusion-requiring bleeding
- Diagnostic
uncertainty (possible VWD, platelet disorder, rare factor deficiency)
15. High-yield Clinical Pearls (Board + Practice)
- BDUC
= diagnosis of exclusion
- Up
to 2/3 of referred bleeding patients end as BDUC
- Heavy
menstrual bleeding = most common presentation
- Normal
labs ≠ normal hemostasis
- Iron
deficiency is a key morbidity
- TXA
= cornerstone therapy in procedures and HMB
- Factor
XIII deficiency & hyperfibrinolysis are common missed diagnoses
- Always
exclude VWD before labeling BDUC
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