Primary Myelofibrosis - Hyperexcision

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Last updated: March 25, 2026Bookmark

Primary myelofibrosis is characterised by the replacement of bone marrow by fibrous tissue. There are abnormal proliferating megakaryocytes and granulocytes that produce cytokines that stimulate fibrosis. The typical presentation is a patient with anaemia, teardrop RBCs, leukoerythroblastosis, and hepatosplenomegaly. No specific treatment exists.

Primary myelofibrosis is the least common myeloproliferative neoplasm. It peaks at > 60 years of age. It affects men more than women.

Definition of terms

Term	Definition
Pre-fibrotic primary myelofibrosis	There is sustained proliferation of megakaryocytes without significant fibrosis (reticulin fibrosis < grade 1)
Overt fibrosis	There is sustained proliferation of megakaryocytes with significant fibrosis (reticulin fibrosis > grade 1)

Grading of myelofibrosis

Grade	Description
MF-0	Scattered linear reticulin with no intersections (normal bone marrow)
MF-1	Loose network of reticulin with many intersections
MF-2	Diffuse and dense reticulin with extensive intersection. Focal bundles of collagen and focal osteosclerosis
MF-3	Diffuse and dense reticulin with extensive intersections. Coarse bundles of collagen and osteosclerosis.

Pathophysiology
- Mutations in JAK2, CALR, or MPL → neoplastic proliferation of megakaryocytes
- Neoplastic megakaryocytes release TGF-B, PDGF, IL-1, EGF, and FGF → fibroblast proliferation, matrix deposition, and endothelial proliferation
Signs and symptoms
- Asymptomatic (30%)
- Fever, weight loss, night sweats
- Fatigue, pallor, breathlessness (due to anemia)
- Splenomegaly (90%, often considered a hallmark)
- Hepatomegaly (50%, portal hypertension develops as a complication and may precede the onset of disease)
- Leukocytosis and thrombocytopenia
- Leukopenia and thrombocytopenia (less common)
- Gouty arthritis
- Renal stones
- Thrombosis
- Hemorrhagic episodes (due to marked thrombocytosis), pruritus, and pulmonary hypertension
Differentials
- Polycythaemia vera
- Essential thrombocythaemia
- Myelodysplastic syndrome
- AML
- ALL
- CML
- Hyperparathyroidism
- SLE
- Vitamin D deficiency
- Systemic sclerosis
Investigations
- Complete Blood Count
  - Anemia
  - Leukopenia
  - Leukocytosis
  - Thrombocytosis
- Peripheral Blood Film
  - Leukoerythroblastosis with teardrop RBCs
  - Large platelets
  - Blasts
  - Pegler-huet cells
- Trephine biopsy
  - Dry tap (30%)
  - Patchy hematopoietic cellularity
  - Reticulin fibrosis
  - Megakaryocytes present in clusters (may be dysplastic)
  - Distended marrow sinusoid (frequently containing intravascular hematopoiesis)
- Molecular studies to detect JAK2, CALR, MPL, BCR-ABL
  - BCR-ABL: negative
  - JAK2 V617F mutations: positive (50-60%)
  - CALR mutations: positive (25-20%) – better prognosis
  - MPL mutation: positive (5-10%)
  - Triple-negative mutation for JAK2, CALR, AND MPL: positive (8-12%)
  - Other mutations in ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2 or SR3B1: positive
  - Karyotype: del(20q), del(13q) in 50% of cases
Treatment
- Splenectomy to reduce symptoms
- Ruxolitinib has some efficacy in treating constitutional symptoms
- A bone marrow transplant is the only definitive cure

Reference Intervals ›

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

Calculator ›

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