Haemophilia is an X-linked recessive clotting disorder that is commonly diagnosed in infant males with haemorrhage or prolonged bleeding time. Symptoms are rarely seen in women due to their heterozygosity.
Classification of haemophilia
Classification Description Haemophilia A (classic haemophilia) X-linked recessive deficiency of factor VIII Haemophilia B (Christmas disease) X-linked recessive deficiency of factor IX Haemophilia C (Rosenthal syndrome) Autosomal recessive deficiency of factor XI
Classification of haemophilia according to severity
Classification Description Mild 5 – 10% of normal clotting factor levels Moderate 1 – 5% of normal clotting factor levels Severe < 1% of normal clotting factor levels. This makes up almost half of the cases.
Signs and symptoms
Haemarthrosis
80% of haemorrhages in patients with haemophilia
Painful, erythematous , stiff, and swollen joint
Affects the knees, ankles and elbows
Requires temporary immobilisation
Ecchymosis
Easy bruising
No clear trauma
Prolonged bleeding after circumcision, surgery, or a dental procedure
Muscular haematoma
15% of haemorrhages in patients with haemophilia
Can cause compartment syndrome
Epistaxis
Melaena and haematemesis
Intracranial bleeding in neonates
Differentials
Investigations
Complete blood count for anaemia and thrombocytopaenia
aPTT
PT to rule out extrinsic and common coagulation pathway pathologies
Liver function tests to rule out liver synthesis dysfunction
Mixing studies: the sample plasma is mixed with normal plasma for two hours
aPTT corrects in inherited clotting factor deficiency
aPTT will not correct in acquired haemophilia due to clotting factor antibodies
Factor VIII and IX assays
Factor VIII and IX gene mutation analysis
vWF antigen testing to rule out von Willebrand disease
Imaging for haematomas
Treatment
Avoid contact sports
Avoid NSAIDs and intramuscular injections
Physiotherapy
Pressure and elevation of musculocutaneous injuries
Recombinant factor VIII and factor IX concentrates
A patient may receive 1 – 3 infusions per week, for a minimum of 45 weeks in the year
Antibodies are more likely to develop in haemophilia A than in haemophilia B
Can also be given during acute bleeding or as prophylaxis
Desmopressin for acute bleeding in mild haemophilia A
Transiently increases factor VIII levels
Tranexamic acid can be considered for severe haemorrhage
Complications
Tranfusion-related infections, e.g. HIV and hepatitis C
Compartment syndrome
Arthropathy
Intracranial and gastrointestinal haemorrhage
Biochemistry
ACTH P: <80 ng/L ALT P: 5–35 U/L Albumin P: 35–50 g/L Aldosterone P: 100–500 pmol/L Alk. phosphatase P: 30–130 U/L α-Amylase P: 0–180 IU/dL α-Fetoprotein S: <10 kU/L Angiotensin II P: 5–35 pmol/L ADH P: 0.9–4.6 pmol/L AST P: 5–35 U/L Bicarbonate P: 24–30 mmol/L Bilirubin P: 3–17 μmol/L BNP P: <50 ng/L CRP P: <10 mg/L Calcitonin P: <0.1 mcg/L Calcium (ionized) P: 1.0–1.25 mmol/L Calcium (total) P: 2.12–2.60 mmol/L Chloride P: 95–105 mmol/L Cholesterol P: <5.0 mmol/L VLDL P: 0.128–0.645 mmol/L LDL P: <2.0 mmol/L HDL P: 0.9–1.93 mmol/L Cortisol AM P: 450–700 nmol/L Cortisol Midnight P: 80–280 nmol/L CK ♂ P: 25–195 U/L CK ♀ P: 25–170 U/L Creatinine P: 70–100 μmol/L Ferritin P: 12–200 mcg/L Folate S: 2.1 mcg/L FSH P: 2–8 U/L ♂; >25 menopause GGT ♂ P: 11–51 U/L GGT ♀ P: 7–33 U/L Glucose (fasting) P: 3.5–5.5 mmol/L Growth hormone P: <20 mu/L HbA1C (DCCT) B: 4–6% HbA1C (IFCC) B: 20–42 mmol/mol Iron ♂ S: 14–31 μmol/L Iron ♀ S: 11–30 μmol/L Lactate (venous) P: 0.6–2.4 mmol/L Lactate (arterial) P: 0.6–1.8 mmol/L LDH P: 70–250 U/L LH P: 3–16 U/L Magnesium P: 0.75–1.05 mmol/L Osmolality P: 278–305 mosmol/kg PTH P: 0.8–8.5 pmol/L Potassium P: 3.5–5.3 mmol/L Prolactin ♂ P: <450 U/L Prolactin ♀ P: <600 U/L PSA P: 0–4 mcg/mL Protein (total) P: 60–80 g/L Red cell folate B: 0.36–1.44 μmol/L Renin (erect) P: 2.8–4.5 pmol/mL/h Renin (recumbent) P: 1.1–2.7 pmol/mL/h Sodium P: 135–145 mmol/L TBG P: 7–17 mg/L TSH P: 0.5–4.2 mU/L T4 P: 70–140 nmol/L Free T4 P: 9–22 pmol/L TIBC S: 54–75 μmol/L Triglycerides P: 0.50–2.3 mmol/L T3 P: 1.2–3.0 nmol/L Troponin T P: <0.1 mcg/L Urate ♂ P: 210–480 μmol/L Urate ♀ P: 150–390 μmol/L Urea P: 2.5–6.7 mmol/L Vitamin B12 S: 0.13–0.68 nmol/L Vitamin D S: 50 nmol/L
Arterial Blood Gases
pH 7.35–7.45 PaCO₂ 4.7–6.0 kPa PaO₂ >10.6 kPa Base excess ±2 mmol/L
Urine
Cortisol (free) <280 nmol/24h Hydroxyindole acetic acid 16–73 μmol/24h Hydroxymethylmandelic acid 16–48 μmol/24h Metanephrines 0.03–0.69 μmol/mmol cr. Osmolality 350–1000 mosmol/kg 17-Oxogenic steroids ♂ 28–30 μmol/24h 17-Oxogenic steroids ♀ 21–66 μmol/24h 17-Oxosteroids ♂ 17–76 μmol/24h 17-Oxosteroids ♀ 14–59 μmol/24h Phosphate (inorganic) 15–50 mmol/24h Potassium 14–120 mmol/24h Protein <150 mg/24h Protein/creatinine ratio <3 mg/mmol Sodium 100–250 mmol/24h
Haematology
WCC 4.0–11.0 ×10⁹/L RBC ♂ 4.5–6.5 ×10¹²/L RBC ♀ 3.9–5.6 ×10¹²/L Hb ♂ 130–180 g/L Hb ♀ 115–160 g/L PCV ♂ 0.4–0.54 L/L PCV ♀ 0.37–0.47 L/L MCV 76–96 fL MCH 27–32 pg MCHC 300–360 g/L RDW 11.6–14.6% Neutrophils 2.0–7.5 ×10⁹/L (40–75%) Lymphocytes 1.0–4.5 ×10⁹/L (20–45%) Eosinophils 0.04–0.44 ×10⁹/L (1–6%) Basophils 0–0.10 ×10⁹/L (0–1%) Monocytes 0.2–0.8 ×10⁹/L (2–10%) Platelets 150–400 ×10⁹/L Reticulocytes 0.8–2.0% / 25–100 ×10⁹/L Prothrombin time 10–14 s APTT 35–45 s
Paediatric
Pulse Rate (bpm) Neonate 140–160 Infant <1yr 120–140 1–5 years 110–130 5–12 years 80–120 >12 years 70–100 Respiratory Rate (tachypnoea) 0–2 months ≥60/min 2–12 months ≥50/min 1–5 years ≥40/min >5 years ≥30/min Blood Pressure (mmHg) Term 65/45 1 year 75/50 4 years 85/60 8 years 95/65 10 years 100/70 Weight Formulas 3–12 months (a + 9)/2 kg 1–6 years 2a + 8 kg >6 years (7a − 5)/2 kg Haemoglobin (g/dL) Term newborn 13–20 1 month 11–18 2 months 10–15 1–2 years 10–13 >2 years 11–14 MUAC (6 months–5 years) Obese >17.5 cm Normal 13.5–17.4 cm At risk 12.5–13.4 cm Moderate malnutrition 11.5–12.4 cm Severe malnutrition <11.5 cm Developmental Milestones Social smile 1.5 months Head control 4 months Sits unsupported 7 months Crawls 10 months Stands unsupported 10–12 months Walks 12–13 months Talks 18 months CSF WBC (/mm³) Term newborn 0–25 >2 weeks 0–5
