Indication for thrombophilia screening
- REcurrent venous thrombosis
- Venous thrombosis before age 45
- Thrombosis at unusual site: portal vein, cavernous sinus, hepatic vein
- FHx of VTE
Tests for thrombophilia
- FBE and ESR
- Factor V leiden
- APLS Abs
- Antithrombin
- Protein C and S
- Prothrombin gene mutation
- Plasma homocysteine
- Occasional PNH work up via flow cytometry
- Occasional factor 3 and VWF levels
PRV Sx
- Vascular problems: TIA, Angina etc
- Nose bleeds
- PUD
- Splenomegaly
- Itch after showering
- Gout
Causes of PRV
Primary - JAK2 mutation
Secondary:
Increased EPO:
- REnal: PCKD, tumor
- Hepatoma
- Cerebellat hemangioma
- UTerine myoma
- Viralising syndroms
- Cushings
- Phaeo
- Self injection of EPO
Hypoxic states:
- Chronic lung disease
- OSA
- Congenital Heart disease
- Abnormal haemoglobin
- Carbon monoxide positoning
Relative
-Smoking
Dehydration
-Stress polycythemia
Ix for PRV
- JAK2 mutation
- Splenomegaly
- Normal PaO2
- Leukocytosis, thrombocytosis
- Low or normal EPO
- Rule out secondary causes (renal, tumors, hypoxia)
Mx of PRV
Aim:
-Lower Haematocrit <0.42 women and <0.45 in men
- Treat underlying cause
- Phlebotomy
- Aspirin to reduce thrombosis risk
- Hydroxyurea if high risk of thrombosis
- IFN - alpha second line (Pregnant women and symptomatic splenomegaly)
- Pruritis: IFN-alpha, psoralen, UV light therapy
- Monitor for hyperuricemia
CAuses of myelofibrosis
Non malignant
- SLE
- HIV
- Renal osteodystrophy
- TB
- Hyperparathyroidism
MAlignant
- CML/myeloproliferative disorders
- Acute leukemia
- Lymphoma
- MM
- Metastatic carcinoma
myelofibrosis prognosis
4-5 years
Ix myelofibrosis
FBE
Blood film: teardrop poikilocytes, leukoerythroblastic picture
Bone marrow Bx
Look for potential causes
Mx myelofibrosis
Supportive
- Blood transfusions
- Hydroxyurea for organomegaly and thrombocytosis
- Folate and B12 replacemeny
- Treat hyperuricemia
- Splenectomy if massive
- JAK2 kinase inhibitor to reduce spleen volume
Curative
-BMAT
ET Sx
- Thromboembolism
- Bleeding
- Poor memory
- Erythromelalgia (painful red extremities)
- Migraine
- Mild splenomegaly
ET IX
- Exclude reactive thrombocytosis
- Bone marrow Bx - Rule out CML, check for JAK2 mutation
- Cyrogenetic studies for CML
ET MX
Asymptomatic and platelets >1 million: no treatment
-Bleeding risk higher with platelets >1 mill and thrombosis risk higher if <1 mill
Symptomatic:
- Aspirin
- Hydroxyurea
- IFN-alpha
- Anagrelide
Complicatins after treatment of haem malignancies
- Secondary malignancy
- Osteoporsis
- Cardiac disease
- Neurocognitive defects
- Lungs: ILD, bronchiolitis obliterans. COP
- Endo: infertility, early menopause
CML Ix
FBE
-Usually basophilia and eosinophilia
PHilidelphia chromosome
CML Tx
Imatinib
-SE: myalgia, hepatotoxicity, fluid retention
BMAT
