Polycythemia is an abnormal increase in red blood cell mass. Causes of polycythemia include a true increase in RBCs -Primary bone marrow problem or Secondary to other disorder ie a physiologic response to hypoxia or to a deranged and increased erythropoetin production.
Primary bone marrow problem –Polycythemia vera ( PV) Exon 12 mutations.
Secondary to other disorder ie a physiologic response to hypoxia or to a deranged and increased erythropoetin production -Hypoxia driven Central hypoxic process Chronic lung disease Rt to Lt cardiopulmonary vascular shunts Carbon monoxide poisoning Smokers erythrocytosis Hypoventilation syndromes including sleep apnoea Local renal hypoxia Renal artery stenosis End-stage renal disease Hydronephrosis Renal cysts- polycytic kidney disease.
Pathological EPO production Tumours Hepatocellular carcinoma Renal cell cancer Cerebellar hemangioblastoma Parathyroid carcinoma/ adenomas Uterine leiomyomas Phaeochromocytoma Meningioma.
Exogenous EPO Drug associated Treatment with androgen preparations Post renal transplant erythrocytosis Idiopathic erythrocytosis.
A decrease in plasma volume –Apparent polycythaemia-Raised haematocrit and Hb conc with a normal cell mass. Due to low plasma volume. Heavy smoking Heavy alcohol consumption hypertension particularly thiazide diuretic use Common in obese men.
What happens –Hct is a measurement of the fractional volume of the RBCs Hct is an important indicator of body’s state of hydration , anaemia or severe blood loss as well as the blood’s capacity to transport oxygen Raised Hct impairs tissue oxygen delivery due to the effects of hyperviscocity A decreased Hct can be due to either overhydration ( which causes incd plasma volume ) or a decrease in the number of of RBCs caused by anaemia or blood loss
Why important –Increased risk of Venous / Arterial Thromboembolic disease.
Patients with raised haematocrit ( Hct ) that is > 0.52 in males > 0.48 in females should be investigated Persistent is generally considered as 4 to 6 weeks.
Features of hyperviscocity – Fatigue + headache + blurred vision + slow ability to think Night sweats Tinnitus Bone pain Itching – particularly after bathing Erythromelalgia- burning sensation fingers/ toes Splenomegaly Weight loss Dizziness or light headedness Bruising , bleeding or clotting.
Polycythemia rubra vera (PV ) –Polycythemia Vera ( PV ) is a Philadelphia chromosome negative myeloproliferative neoplasm Manifests as clonal stem-cell proliferation of red blood cells , WBCs and platelets Increased RBC mass causes hyperviscocity which increases the risk of thrombosis with a reduced life expectancy About 96 % of patients have mutation of the Janus kinase 2 ( JAK2 ) gene. Median age of presentation is 60 yrs – slight male predominance in all races and ethnicity Uncommon in people < 30 Seen more commonly in Jews of Eastern European descent than among other European and Asian populations.
Findings suggestive of PV –Leukocytosis ( modest but can be non-specific ) WBC > 15 -predicts bad overall prognosis Neutrophilia Thrombocytosis – modest MCV- usually low Low MCV + Normal Hb + iron deficiency Blood film- atypical features ○ circulating blasts ○ leucoerythroblastic features ○ monocytosis Elevated uric acid and Vit B12 Ferritin – low ferritin levels are common in PV patients and iron deficiency can mask the presentation.
PV complications – Thrombosis is the most common complication of PV -one half to three quarters of these events are arterial Complications of thrombosis include ○ ischaemic stroke and transient ischaemic attacks Life expectancy increases ( 20 yrs in average ) with treatment ( PV ) PV patients need regular haematology f/u as 2-8 % cases can transform into myelofibrosis and about 1-3 % can transform to AML People with secondary causes may have increased risk of thrombosis but this is substantially less than for people with PV.
Assessment in primary care –History and examination H/O smoking and thrombosis ask about h/o ○ chronic lung disease ○ Obstructive sleep apnoea ○ congenital cardiac disease h/o arterial or venous thrombosis any other arterial risk factors ask about smoking , alcohol full list of medications- particularly thiazide diuretics any symptoms suggestive of hyperviscocity ask about family h/o myeloprolifertive disease.
Confirm finding with repeat FBC over time – is this true or relative / spurious polycythemia .
FBC – repeat over time & uncuffed if possible Hct results can be affected by the settling of RBCs in the collection device Blood film U/E , LFT Ferritin – a high haematocrit despite a low ferritin indicates polycytnemia vera – do not start iron therapy Bl sugar , Hba1x Lipid profile JAK2 mutation testing – if available Serum erythropoeitin level ( EPO ) pulse oximetry ( secondary causes ).
Modify and address secondary risk factors-review CV risk factors e, g smoking change thiazide diuretic to an alternative if possible screen for diabetes do not initiate aspirin therapy unless PRV diagnosis is established.
Secondary causes –Secondary cause found and corrected for e.g changed medication- diuretics / smoking etc Hct < 0.54- monitor FBC every 3 months Hct > 0.54- refer haematology. No secondary cause found-refer haematology.
Referral –Haematocrit can be lowered -leading to reduced CV events and ↑ survival. The aim differs based on the diagnosis for e.g in PV the target haematocrit is 0.45 in secondary and apparent polycythemia the target is 0.54 These may vary based on local protocol and individual circumstances.
Urgent referral –significantly raised Hct which is in males > 0.600 females > 0.560 with no h/o congenital cyanotic heart disease.
Also consider an urgent or routine referral based on clinical situation-persistently raised Hct which is in males > 0.510 and females > 0.48 and a h/o ○ recent arterial / venous thrmbosis Polycythemia presenting with hyperviscosity symptoms ○ neurological symptoms ○ visual loss ○ abnormal bleeding ○ raised WBC count and / or raised platelet count Guidance varies for men the threshold ie the Hct at which a referral should be considered is from 0.51 to 0.52 . You may consider checking your local hematology guideline.
All suspected primary polycythemias sould always be referred to haematology Secondary causes which cannot be corrected in primary care.
LINKS AND RESOURCES – FOR PROFESSIONALS
Credible Meds via https://www.crediblemeds.org/
Credible Meds app https://crediblemeds.org/blog/smartphone-apps-crediblemeds-now-available/
Medscape drug interaction checker https://reference.medscape.com/drug-interactionchecker
Safe drugs in Brugada Syndrome https://www.brugadadrugs.org/
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