History

Fact Explanation
Introduction Secondary polycythaemia is increased haemoglobin concentration in blood above the upper normal range(according to patient's age and sex) due to increased erythropoiesis secondary to another cause( which are driven independant of the haematopoietic stem cells in the bone marrows) [1].
Lethargy, confusion, headache, dizziness These symptoms are due to central nervous system disturbances with hyperviscosity causing poor perfusion[2]
Features suggestive of arterial thrombosis With the hyperviscosity there is a increased risk of thrombotic complications. Arterial thrombotic complications can damage various systems giving specific features of hypoperfusion. Eg; In cardiac complications, patient will present with chest pain, difficulty in bresthing, dizziness, sweating and other features of myocardial infarction/ angina[10]. If thrombotic complications occur in central nervous system, patient will have seizures, paralysis and paresthesia like features[9]. If thrombosis occur in a artery supplying to limbs, patients will present with acute limb ischemia( sever pain at rest, coldness, limited movements, numbness) following features of occlusive arterial disease like pain starting few minutes after initiating walking, pain relief with resting and reproduce with walking in a same distance[8].
Features suggestive of venous thrombosis In deep vein thrombosis patient will present with acute onset severe pain, swelling, redness and warmth of the limb. Hepatic venous thrombosis will present with abdominal distension(ascites), features of liver insufficiency like nausea, vomiting, loss of appetite, yellowish discoloration of eyes, generalized swelling and gastrointestinal bleeding( either as haemoptysis/ malena)[11]. In cerebral venous thrombosis patient will be confused, drowsy, may develop seizures due to cerebral venous disease[3]. Visual disturbances can occur due to retinopathy.This visual problems is call 'slow- flow retinopathy'.
Severe continuous small joint pain Patients will present with symptoms of gout as a result of increased uric acid production. Gout mainly affects big toe[12].
Past history of congenital heart disease or history suggestive of it( blush discoloration, squatting on exercise) Polycythemia can occur secondary to cyanoic congenital heart diseases like tetralogy of fallot and transposition of great arteries as there is poor oxygenation of the blood causing poor tissue perfusion wich ultimately leads to increased eruthropoietin production to compensate the hypoxaemic csituation[4][13].
Feature suggestive of chronic lung disease like difficulty in breathing, wheezing, acute exacerbations, progressive reduction of working capacity. Chronic pulmonary disease( eg: Chronic Obstructive Pulmonary Disease) can cause progressive ariway obstruction and poor alveolar ventialtion dyspite of good alveolar perfusion. So oygenation of deoxygenated blood in lungs will be poor leading to increased erythropoietin production to compensate the need causing increased red blood cell production[2]
Recidence In high altitudes there is less oxygen percentage in air compare to other areas. So air coming to alveoli will contain less oxygen causing poor exchange with blood. This induce hypoxic condition to a certain extend causing increase production of erythropoietin to increase the red cell mass which can catch more oxygen and this leads to polycythemia[14].
History suggestive of sleep apnoea like snoring loudly in sleep, day time sleepiness, poor sleep, morning headache and reduced performance. In obese people there will be an intermittent closure/ collapse of the pharyngeal air way causing apnoic episodes during sleep. This conditionn leads to periodic alveolar hypoventilation. So periodic hypoxia in long term can induce erythropoietin production causing polycythemia[15].
history of loss of weight, loss of appetite, red coloured urine, back pain like symptoms suggestive of renal pathology. In disease conditions affecting kidneys like renal tumours, hydronephrosis and renal cysts there is associated secondary polycythemia by inappropriate increase in erythropoietin production[7].
Loss of weight, loss of appetite, body swelling, yellowish dyscoloration of eyes giving evidence of liver pathology. In hepatocellular carcinoma there is an increased erythropoietin in blood as hepatocellular carcinomal cells leads to erythropoietin production. This stimulates excessive increase production of red blood cells from bone marrows causing polycythemia[16].
recent symptoms or past history of acute breathlessness, pleuritic type chest pain, haemoptysis, dizziness and syncopy As patients are at risk of pulmonary embolism with increased risk of venous thrombo embolism following polycythemia theses presentation is very important[3].
References
  1. JEPSON JH. Polycythemia: diagnosis, pathophysiology and therapy. I. Can Med Assoc J [online] 1969 Feb 8, 100(6):271-277 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1945593
  2. TRIPATHY S, PANDA SS, RATH B. Phlebotomy for rapid weaning and extubation in COPD patient with secondary polycythemia and respiratory failure Lung India [online] 2010, 27(1):24-26 [viewed 26 September 2014] Available from: doi:10.4103/0970-2113.59264
  3. BHATT VR. Secondary Polycythemia and the Risk of Venous Thromboembolism J Clin Med Res [online] 2014 Oct, 6(5):395-397 [viewed 26 September 2014] Available from: doi:10.14740/jocmr1916w
  4. ROSE SS, SHAH AA, HOOVER DR, SAIDI P. Cyanotic Congenital Heart Disease (CCHD) with Symptomatic Erythrocytosis J Gen Intern Med [online] 2007 Dec, 22(12):1775-1777 [viewed 26 September 2014] Available from: doi:10.1007/s11606-007-0356-4
  5. MOORE-GILLON J. Smoking--a major cause of polycythemia. J R Soc Med [online] 1988 Jul, 81(7):431 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1291690
  6. BEDELL GN, WILSON WR, SEEBOHM PM. Pulmonary Function in Obese Persons J Clin Invest [online] 1958 Jul, 37(7):1049-1060 [viewed 26 September 2014] Available from: doi:10.1172/JCI103686
  7. BHAT RA, KHAN I, KHAN I, MIR MA. Polycythemia, increased erythropoietin levels in a patient with renal lymphoma Adv Biomed Res [online] :147 [viewed 26 September 2014] Available from: doi:10.4103/2277-9175.135417
  8. CALLUM K, BRADBURY A. Acute limb ischaemia BMJ [online] 2000 Mar 18, 320(7237):764-767 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1117769
  9. AHMAD F, ASIMI R, RASOOL S. Polycythemia and chorea Ann Saudi Med [online] 2009, 29(1):63-64 [viewed 26 September 2014] Available from: doi:10.4103/0256-4947.5181
  10. STERGIOPOULOS K, BRENNAN JJ, MATHEWS R, SETARO JF, KORT S. Anabolic steroids, acute myocardial infarction and polycythemia: A case report and review of the literature Vasc Health Risk Manag [online] 2008 Dec, 4(6):1475-1480 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663437
  11. VELDMAN A, NOLD MF, MICHEL-BEHNKE I. Thrombosis in the critically ill neonate: incidence, diagnosis, and management Vasc Health Risk Manag [online] 2008 Dec, 4(6):1337-1348 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663458
  12. LEWIS JG. Gout and the Haemoglobin Level in Patients with Cardiac and Respiratory Disease Br Med J [online] 1961 Jan 7, 1(5218):24-26 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1952699
  13. SOMERVILLE J. GOUT IN CYANOTIC CONGENITAL HEART DISEASE Br Heart J [online] 1961 Jan, 23(1):31-34 [viewed 29 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1017729
  14. SCHREIJER AJ, REITSMA PH, CANNEGIETER SC. High hematocrit as a risk factor for venous thrombosis. Cause or innocent bystander? Haematologica [online] 2010 Feb, 95(2):182-184 [viewed 29 September 2014] Available from: doi:10.3324/haematol.2009.017285
  15. HUKINS CA. Obstructive sleep apnea - management update Neuropsychiatr Dis Treat [online] 2006 Sep, 2(3):309-326 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671821
  16. SAKISAKA S, WATANABE M, TATEISHI H, HARADA M, SHAKADO S, MIMURA Y, GONDO K, YOSHITAKE M, NOGUCHI K, HINO T. Erythropoietin production in hepatocellular carcinoma cells associated with polycythemia: immunohistochemical evidence. Hepatology [online] 1993 Dec, 18(6):1357-62 [viewed 29 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/7694895

Examination

Fact Explanation
Plethoric appearance Patient will have a plethoric appearance with cyanosis( due to incresed de oxygenated haemoglobin level with excess red blood cell production), congenital suffusion and retinal vein engorgement. This appearance will be prominent in face, palms, nailbeds, mucosa and conjunctiva[7].
Signs of arterial thrombotic complications With the hyperviscosity there is a increased risk of thrombotic complications. Arterial thrombotic complications can damage various systems giving specific features of hypoperfusion. Eg; In cardiac complications, patient will in a pain, dyspnoic following myocardial infarctions[3]. If thrombotic complications occur in central nervous system, patient will develop seizures and/ or signs of motor/ sensory impairment and crenial nerve palsy[4]. If thrombosis occur in a artery supplying to limbs, patients will in a severe pain, limb will be discoloured, cold and movements will be limited[5].
Signs of venous thrombotic complications In deep vein thrombosis patient will in a severe pain with out moving affected limb, limb will be swollen, reddish and warm. When hepatic venous thrombosis examination will reveals generalized oedema, ascites, Jaundice due to liver insufficiency[8]. In cerebral venous thrombosis patient will be confuse and drowsy[2].
High blood pressure Patients will have hypertension due to poor tissue perfusion[1].
Nicotin stains in lips/ fingers and cigarette smell during examination Heavy cigarette smoking is a predisposing factor for secondary polycythemia. So these signs will helpful especially if the patient denies cigarette smoking[4].
Features of dehydration Dry skin and mucus membranes, reduced urine out put will give evidence of dehydration which is an cause for relative polycythemia[3].
Respiratory system examination In a COPD patient tachypnoea, use of accessory muscles, hyperinflated lungs, reduced costocondral distance, reduced lung expansion, hyperresonant percussion note will be present[1].
Cardiovascular system examination In cyanotic heart diseases patients will present with cyanosis, finger clubbing and other disease specific features[3]. eg; Tetralogy of fallot- ejection systolic murmur in pulmonary area, hypercyanotic spells
Abdominal examination Splenomegaly is found in majority of patients with polycythemia due to increased red blood cell destruction [9]. Hepatomegaly with features of chronic liver failure( jaundice, ascites, oedema) will present in a hepatocellular carcinoma. Ballatable mass will present in a hydronephrosis, renal cell carcinoma and cystic kidney[6]. All these leads to secondary polycythemia.
Measurement of BMI using height and weight Morbid obesity is a cause for this as it leads to obstructive sleep apnea causing alveolar hypoventilation[5].
References
  1. TRIPATHY S, PANDA SS, RATH B. Phlebotomy for rapid weaning and extubation in COPD patient with secondary polycythemia and respiratory failure Lung India [online] 2010, 27(1):24-26 [viewed 26 September 2014] Available from: doi:10.4103/0970-2113.59264
  2. BHATT VR. Secondary Polycythemia and the Risk of Venous Thromboembolism J Clin Med Res [online] 2014 Oct, 6(5):395-397 [viewed 26 September 2014] Available from: doi:10.14740/jocmr1916w
  3. ROSE SS, SHAH AA, HOOVER DR, SAIDI P. Cyanotic Congenital Heart Disease (CCHD) with Symptomatic Erythrocytosis J Gen Intern Med [online] 2007 Dec, 22(12):1775-1777 [viewed 26 September 2014] Available from: doi:10.1007/s11606-007-0356-4
  4. MOORE-GILLON J. Smoking--a major cause of polycythemia. J R Soc Med [online] 1988 Jul, 81(7):431 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1291690
  5. BEDELL GN, WILSON WR, SEEBOHM PM. Pulmonary Function in Obese Persons J Clin Invest [online] 1958 Jul, 37(7):1049-1060 [viewed 26 September 2014] Available from: doi:10.1172/JCI103686
  6. BHAT RA, KHAN I, KHAN I, MIR MA. Polycythemia, increased erythropoietin levels in a patient with renal lymphoma Adv Biomed Res [online] :147 [viewed 26 September 2014] Available from: doi:10.4103/2277-9175.135417
  7. MICHIELS JJ, INSTITUTE AND FOUNDATION G, EDUCATION THROMBOCYTHEMIA VERA STUDY GROUP FO, EWG.MPN TA. Physiopathology, Etiologic Factors, Diagnosis, and Course of Polycythemia Vera as Related to Therapy According to William Dameshek, 1940-1950 Turk J Haematol [online] 2013 Jun, 30(2):102-110 [viewed 26 September 2014] Available from: doi:10.4274/Tjh.2013.0029
  8. VELDMAN A, NOLD MF, MICHEL-BEHNKE I. Thrombosis in the critically ill neonate: incidence, diagnosis, and management Vasc Health Risk Manag [online] 2008 Dec, 4(6):1337-1348 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663458
  9. WERNIG G, MERCHER T, OKABE R, LEVINE RL, LEE BH, GILLILAND DG. Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant model Blood [online] 2006 Jun 1, 107(11):4274-4281 [viewed 29 September 2014] Available from: doi:10.1182/blood-2005-12-4824

Differential Diagnoses

Fact Explanation
Polycythemia Rubra Vera This is a malignant condition in bone marrow stem cells associated with increased blood cell volume. The condition occurs as a result of a mutation( JAK2 mutation) in a single haemopoietic stem cells. This is a primary cause of polycythemia[2]. secondary polycytemia can occur due to several reasons like high altitude, pulmonary disease with alveolar hypoperfusion(COPD), cardiovascular diseases, heavy smoking with increase in compensatory eruthropoietin, renal disease disease, with some tumours like hepatocellular carcinoma due to inapppropriate increase in erythropoietin. Presence of these causes will helpful in differentiating both conditions[5].
Relative polycythemia Relative polycythemia can caused following stress, cigarette smoking, dehydration, (eg; diarrhoea, severe vomiting, poor fluid intake) and in plasma loss( eg; burns). In here there is reduction of plasma volume concentrating the blood but total red cell volume will be normal[6]. In secondary polycythemia there will be actual increase in production of red cell mass from bone marrows[5].
Chronic myelogenous leukemia This is a condition associated wit clonal proliferation of myeloid cells. They will present with chronic symptoms of weight loss, tiredness, fever, sweats, features of gout and bleeding. Philadelphia chromosome is present in majority of patients[3].In secondary polycythemia there is no genetic association[7].
Myeloid metaplasia In myeloid metaplasia there is hyperplasia of megakaryocytes. It produces platelet derived growth factor causing marrow fibrosis and myeloid metaplasia. Patients will have night sweats, fever, weight loss, splenomegaly and evidence of bone marrow failure( bleeeding, recurrent infections, anaemia) Bone marrow biopsy helpful in diagnosis[4].In secondary Polycythemia there will be features of excessive red cell mass like thromotic complictions and bleeding manifestations. Simple investigation like FBC is helpful in differentiating the diseases[5].
Essential thrombocythaemia In this disease there is a clonal proliferation of megakaryocytes causing continuous increase in platelet levels with poor quality resulting bleeding, arterial/ venous thrombosis and symptoms of microvascular ischemia[1]. In secondary Polycythemia there is increased red blood cell volume. So from simple investigations like full blood count will reveals the different count changes helping the differentiating both conditions[5].
Tetralogy of fallot This is a cyanotic congenital heart disease associated with large VSD, overriding aorta, subpulmonary stenosis and right ventricular hypertrophy. Polycythemia can occur secondary to this cyanoic congenital heart diseases as there is poor oxygenation of the blood causing poor tissue perfusion wich ultimately leads to increased eruthropoietin production to compensate the hypoxaemic csituation. Echocardiogram will helpful in assessing the presence of cardiac abnormalities[8].
Chronic Obstructive Pulmonary Disease Chronic pulmonary disease( eg: Chronic Obstructive Pulmonary Disease) can cause progressive ariway obstruction and poor alveolar ventialtion dyspite of good alveolar perfusion. So oygenation of deoxygenated blood in lungs will be poor leading to increased erythropoietin production to compensate the need causing increased red blood cell production[9[10].
Sleep apnoea In obese people there will be an intermittent closure/ collapse of the pharyngeal air way causing apnoic episodes during sleep. This conditionn leads to periodic alveolar hypoventilation. So periodic hypoxia in long term can induce erythropoietin production causing polycythemia. Patient will give a history suggestive of sleep apnoea like snoring loudly in sleep, day time sleepiness, poor sleep, morning headache and reduced performance[11].
Renal tumour In renal tumours there is associated secondary polycythemia by inappropriate increase in erythropoietin production. Patientd will have loss of weight, loss of appetite,painless haematuria, back pain like symptoms suggestive of renal pathology[12].
Hepatocellular carcinoma In hepatocellular carcinoma there is an increased erythropoietin in blood as hepatocellular carcinomal cells leads to erythropoietin production. This stimulates excessive increase production of red blood cells from bone marrows causing polycythemia.Patient will also have loss of weight, loss of appetite, body swelling, yellowish discoloration of eyes giving evidence of liver pathology[13].
References
  1. BEATRICE JM, GARANITO MP. Essential thrombocythemia: a rare disease in childhood Rev Bras Hematol Hemoter [online] 2013, 35(4):287-289 [viewed 29 September 2014] Available from: doi:10.5581/1516-8484.20130059
  2. SCOTT RB. Treatment of Polycythaemia Rubra Vera Br Med J [online] 1953 May 23, 1(4820):1128-1131 [viewed 20 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2016124
  3. KELLIHER MA, MCLAUGHLIN J, WITTE ON, ROSENBERG N. Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL. Proc Natl Acad Sci U S A [online] 1990 Sep, 87(17):6649-6653 [viewed 20 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC54594
  4. MARKS C, AHMADI M. Agnogenic myeloid metaplasia: role of splenectomy Postgrad Med J [online] 1969 Apr, 45(522):261-265 [viewed 20 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2466587
  5. BHATT VR. Secondary Polycythemia and the Risk of Venous Thromboembolism J Clin Med Res [online] 2014 Oct, 6(5):395-397 [viewed 20 September 2014] Available from: doi:10.14740/jocmr1916w
  6. LAWRENCE JH, BERLIN NI. Relative Polycythemia--The Polycythemia of Stress Yale J Biol Med [online] 1952 Jun, 24(6):498-505 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2599279
  7. JEPSON JH. Polycythemia: diagnosis, pathophysiology and therapy. I. Can Med Assoc J [online] 1969 Feb 8, 100(6):271-277 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1945593
  8. SOMERVILLE J. GOUT IN CYANOTIC CONGENITAL HEART DISEASE Br Heart J [online] 1961 Jan, 23(1):31-34 [viewed 29 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1017729
  9. TRIPATHY S, PANDA SS, RATH B. Phlebotomy for rapid weaning and extubation in COPD patient with secondary polycythemia and respiratory failure Lung India [online] 2010, 27(1):24-26 [viewed 26 September 2014] Available from: doi:10.4103/0970-2113.59264
  10. MACNEE W, CALVERLEY P. Chronic obstructive pulmonary disease o 7: Management of COPD Thorax [online] 2003 Mar, 58(3):261-265 [viewed 29 September 2014] Available from: doi:10.1136/thorax.58.3.261
  11. HUKINS CA. Obstructive sleep apnea - management update Neuropsychiatr Dis Treat [online] 2006 Sep, 2(3):309-326 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671821
  12. BHAT RA, KHAN I, KHAN I, MIR MA. Polycythemia, increased erythropoietin levels in a patient with renal lymphoma Adv Biomed Res [online] :147 [viewed 26 September 2014] Available from: doi:10.4103/2277-9175.135417
  13. SAKISAKA S, WATANABE M, TATEISHI H, HARADA M, SHAKADO S, MIMURA Y, GONDO K, YOSHITAKE M, NOGUCHI K, HINO T. Erythropoietin production in hepatocellular carcinoma cells associated with polycythemia: immunohistochemical evidence. Hepatology [online] 1993 Dec, 18(6):1357-62 [viewed 29 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/7694895

Investigations - for Diagnosis

Fact Explanation
Full blood count Due to excessive production of red blood cells, red blood cell count, haemoglobin, haematocrit and pack cell volume will be high[2].
Total red cell mass and plasma volume measurement This is useful in differentiating absolute polycythemia from relative polycythemia. In absolute polycythemia there will be increase in total red cell mass and normal plasma volume. In relative polycythemia there will ne normal Total red cell mass with reduced plasma volume[7].
Peripheral blood film This will show incresed red cell mass with normochromic and normocytic red blood cells[10].
Serum erythropoietin level This will behigh due to excess production of the hormone[4].
Carboxyhemoglobin levels The level of Carboxyhemoglobin will be high in patients who are smoking cigarette. So this also useful in identifying the primary cause[3].
Assessing hemoglobin-oxygen dissociation curve using oxygen saturation and levels of 2,3-diphosphoglycerate This is useful in identifying haemoglobin affinity in patients. As high affinity can induce excessive erythrocyte production leading to polycythemia[9].
Bone marrow biopsy This will shows hyper cellular bone marrows with prominent megakaryocytes[11].
Ultrasound scan of the abdomen, CT scan/ MRI scan As hepatocellular carcinoma, hydronephrosis, renal cell carcinoma, cystic kidney and some brain tumours( eg; cerebellar haemangioblastoma) can cause secondary polycythemia, these imaging studies will helpful in identifying them and associated other complications[4].
Chest X ray As some chronic lung diseases can cause this condition chest X ray will also helpful. Eg: In COPD patients Chest X ray will show hyperinflated lungs, flat diaphragms and tubular heart[1].
ECG, Echocardiogram As cyanotic congenital heart diseases can lead to polycythemia this is useful in identifying the patients cardiac abnormality and current status[2].
Arterial oxygen saturation measure by Arterial Blood Gas analysis This is useful in identifying hypoxia as a primary cause[8].
Karyotyping Presence of cytoplasmic tyrosine kinase Janus-associated kinase 2(JAK2) mutation in haemopoietic cells will helpful in differentiating Polycythemia Rubra Vera from secondary polycythemia[5][6].
References
  1. TRIPATHY S, PANDA SS, RATH B. Phlebotomy for rapid weaning and extubation in COPD patient with secondary polycythemia and respiratory failure Lung India [online] 2010, 27(1):24-26 [viewed 26 September 2014] Available from: doi:10.4103/0970-2113.59264
  2. ROSE SS, SHAH AA, HOOVER DR, SAIDI P. Cyanotic Congenital Heart Disease (CCHD) with Symptomatic Erythrocytosis J Gen Intern Med [online] 2007 Dec, 22(12):1775-1777 [viewed 26 September 2014] Available from: doi:10.1007/s11606-007-0356-4
  3. MOORE-GILLON J. Smoking--a major cause of polycythemia. J R Soc Med [online] 1988 Jul, 81(7):431 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1291690
  4. BHAT RA, KHAN I, KHAN I, MIR MA. Polycythemia, increased erythropoietin levels in a patient with renal lymphoma Adv Biomed Res [online] :147 [viewed 26 September 2014] Available from: doi:10.4103/2277-9175.135417
  5. HUSSEIN K, GRANOT G, SHPILBERG O, KREIPE H. Clinical utility gene card for: familial polycythaemia vera Eur J Hum Genet [online] 2013 Jun [viewed 20 September 2014] Available from: doi:10.1038/ejhg.2012.216
  6. MCLORNAN D, PERCY M, MCMULLIN MF. JAK2 V617F: A Single Mutation in the Myeloproliferative Group of Disorders Ulster Med J [online] 2006 May, 75(2):112-119 [viewed 20 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1891745
  7. BENTLEY DP, THOMSON WH, NAPIER JA. An improved method for the diagnosis of polycythaemia. J Clin Pathol [online] 1978 Oct, 31(10):956-959 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1145459
  8. MOORE-GILLON JC, TREACHER DF, GAMINARA EJ, PEARSON TC, CAMERON IR. Intermittent hypoxia in patients with unexplained polycythaemia. Br Med J (Clin Res Ed) [online] 1986 Sep 6, 293(6547):588-590 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1341379
  9. PERCY MJ, BUTT NN, CROTTY GM, DRUMMOND MW, HARRISON C, JONES GL, TURNER M, WALLIS J, MCMULLIN MF. Identification of high oxygen affinity hemoglobin variants in the investigation of patients with erythrocytosis Haematologica [online] 2009 Sep, 94(9):1321-1322 [viewed 26 September 2014] Available from: doi:10.3324/haematol.2009.008037
  10. AHMAD F, ASIMI R, RASOOL S. Polycythemia and chorea Ann Saudi Med [online] 2009, 29(1):63-64 [viewed 26 September 2014] Available from: doi:10.4103/0256-4947.51815
  11. LUCIE NP, YOUNG GA. Marrow cellularity in the diagnosis of polycythaemia. J Clin Pathol [online] 1983 Feb, 36(2):180-183 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC498146

Investigations - Fitness for Management

Fact Explanation
Full blood count This is useful in assessing the patients polycythemic condition. The haematocrit should be monitored and has to be maintained below 0.45. [1][6].
arterial oxygen saturation This is useful in assessing the oxygen saturation of the patient as hypoxia is common[2].
Coagulation profile (PT/INR and APTT) Basic coagulation tests such as PT/INR and APTT has to be carried out to see any procoagulabilty which could be detected by them[7].
Thormbophilic screening studies (Hams test, Factor V laden, Protein C, Protein S) Thrombophilic screening studies such as Hams test, Factor V laden, Protein C, Protein S has to be done to detect other concurrent prothrombotic diseases[5].
ANA, ds DNA Possibility of connective tissue disorder has to excluded[4].
References
  1. ROSE SS, SHAH AA, HOOVER DR, SAIDI P. Cyanotic Congenital Heart Disease (CCHD) with Symptomatic Erythrocytosis J Gen Intern Med [online] 2007 Dec, 22(12):1775-1777 [viewed 26 September 2014] Available from: doi:10.1007/s11606-007-0356-4
  2. MOORE-GILLON JC, TREACHER DF, GAMINARA EJ, PEARSON TC, CAMERON IR. Intermittent hypoxia in patients with unexplained polycythaemia. Br Med J (Clin Res Ed) [online] 1986 Sep 6, 293(6547):588-590 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1341379
  3. T ROCHA A, F PAIVA E, LICHTENSTEIN A, MILANI R JR, CAVALHEIRO-FILHO C, H MAFFEI F. Risk-assessment algorithm and recommendations for venous thromboembolism prophylaxis in medical patients Vasc Health Risk Manag [online] 2007 Aug, 3(4):533-553 [viewed 29 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291339
  4. LANGE A. Evaluation of the simultaneous estimation of anti-dsDNA and anti-ssDNA antibodies for clinical purposes. Clin Exp Immunol [online] 1978 Mar, 31(3):472-481 [viewed 30 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1541258
  5. MERRIMAN L, GREAVES M. Testing for thrombophilia: an evidence-based approach Postgrad Med J [online] 2006 Nov, 82(973):699-704 [viewed 30 September 2014] Available from: doi:10.1136/pgmj.2006.048090
  6. MCMULLIN MF. Diagnosis and management of congenital and idiopathic erythrocytosis Ther Adv Hematol [online] 2012 Dec, 3(6):391-398 [viewed 30 September 2014] Available from: doi:10.1177/2040620712458947
  7. CHHABRA G, SHARMA S, SUBRAMANIAN A, AGRAWAL D, SINHA S, MUKHOPADHYAY AK. Coagulopathy as prognostic marker in acute traumatic brain injury J Emerg Trauma Shock [online] 2013, 6(3):180-185 [viewed 30 September 2014] Available from: doi:10.4103/0974-2700.115332

Investigations - Followup

Fact Explanation
Full blood count This is useful in assessing the patients respond to the treatments by looking at blood counts[2]
Ultrasound scan , CT/ MRI brain These tests are useful in follow up if identified any primary cause as mentioned in the diagnosis section . Also if the patient present with thrombotic complications in central nervous system these test are useful[3].
ECG and Echocardiogram As cyanotic congenital heart diseases can lead to polycythemia this is useful in identifying the patients cardiac abnormality and current status in follow up. Also if the patient present with thrombotic complicatients in cardiovascular system these tests are helpful in confirmation and assessing the patients current condition[2].
Doppler studies If patient present with peripheral thrombotic complications causing limb ischemia doppler studies will useful in assessing the current condition and in deciding the further treatment[4].
References
  1. BHAT RA, KHAN I, KHAN I, MIR MA. Polycythemia, increased erythropoietin levels in a patient with renal lymphoma Adv Biomed Res [online] :147 [viewed 26 September 2014] Available from: doi:10.4103/2277-9175.135417
  2. ROSE SS, SHAH AA, HOOVER DR, SAIDI P. Cyanotic Congenital Heart Disease (CCHD) with Symptomatic Erythrocytosis J Gen Intern Med [online] 2007 Dec, 22(12):1775-1777 [viewed 26 September 2014] Available from: doi:10.1007/s11606-007-0356-4
  3. BHAT RA, KHAN I, KHAN I, MIR MA. Polycythemia, increased erythropoietin levels in a patient with renal lymphoma Adv Biomed Res [online] :147 [viewed 26 September 2014] Available from: doi:10.4103/2277-9175.135417
  4. ONMEZ H, CINGOZ HT, KUCUKSEN S, ANLIACıK E, YAşAR O, YILMAZ H, SALLI A. Bilateral upper-extremity deep vein thrombosis following central cord syndrome J Spinal Cord Med [online] 2013 May, 36(3):243-246 [viewed 26 September 2014] Available from: doi:10.1179/2045772313Y.0000000096

Investigations - Screening/Staging

Fact Explanation
Full blood cunt This also useful in screening as it gives an idea about the blood counts but total red cell mass measurement should be done with this to confirm the condition[1][2].
References
  1. ROSE SS, SHAH AA, HOOVER DR, SAIDI P. Cyanotic Congenital Heart Disease (CCHD) with Symptomatic Erythrocytosis J Gen Intern Med [online] 2007 Dec, 22(12):1775-1777 [viewed 26 September 2014] Available from: doi:10.1007/s11606-007-0356-4
  2. BENTLEY DP, THOMSON WH, NAPIER JA. An improved method for the diagnosis of polycythaemia. J Clin Pathol [online] 1978 Oct, 31(10):956-959 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1145459

Management - General Measures

Fact Explanation
Health education Patient should be educated regarding the disease, primary cause for the disease, symptoms associated with, possible complications, available treatment options and prognosis[2].
Stop smoking Heavy smoking is a cause for secondary polycythemia and also a for Chronic Obstructive Lung Disease progression. So patients should be adviced to stop smoking[1].
Reduced body weight Morbid obesity is a cause for secondary thrombocytopenia as it leads to obstructive sleep apnea causing alveolar hypoventilation. So patient should be advised to maintain body weight in normal range for height. Increasing quality of the diet( balanced diet need to be taken) while reducing the quantity and regular physical exercise is advisable[3].
DVT prophylaxis Can be non pharmacological and pharmacology modalities. Non pharmacological moralities are good hydration, adequate mobilization of the patient, limb physiotherapy and thrombo embolic detergenic stocking. The main pharmacological propylaxis is low molecular weight heparin in high risk patients if no contraindication (eg: Sub cutaneous enoxaparin 0.5mg/kg/day).[4]
ABC management in emergency situation The possible emergencies in patients with polycythaemia are pulmonary embolism, massive stoke, myocardial infarction, cerebral venous thrombosis, mesenteric infarction. In these circumstances ABC management is essentially life saving. Airway has to be secured : foreign body has to be removed, maneuvers such as jaw thrust, chin lift and head tilt has to done. Oral air way, laryngeal mask air way and intubation would be beneficial if not corrected by simple maneuvers. Breathing has to be assessed and respiratory support should be given with ambu ventilation or via a ventilator. Circulation has to be assessed and fluid resuscitation with inotrope support has to started as indicated.
References
  1. MOORE-GILLON J. Smoking--a major cause of polycythemia. J R Soc Med [online] 1988 Jul, 81(7):431 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1291690
  2. JEPSON JH. Polycythemia: diagnosis, pathophysiology and therapy. I. Can Med Assoc J [online] 1969 Feb 8, 100(6):271-277 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1945593
  3. BEDELL GN, WILSON WR, SEEBOHM PM. Pulmonary Function in Obese Persons J Clin Invest [online] 1958 Jul, 37(7):1049-1060 [viewed 26 September 2014] Available from: doi:10.1172/JCI103686
  4. CAYLEY WE JR. Preventing deep vein thrombosis in hospital inpatients BMJ [online] 2007 Jul 21, 335(7611):147-151 [viewed 30 September 2014] Available from: doi:10.1136/bmj.39247.542477.AE
  5. THIM T, KRARUP NH, GROVE EL, ROHDE CV, LøFGREN B. Initial assessment and treatment with the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach Int J Gen Med [online] :117-121 [viewed 30 September 2014] Available from: doi:10.2147/IJGM.S28478

Management - Specific Treatments

Fact Explanation
Venesection(phlebotomy) Venesection is aimed to reduce haematocrit value less then 0.45 to reduce the risk of thrombosis.This is useful in patients with symptoms like dizziness, dyspnoea or angina, with increased haematocrit level more the 0.56 and in patients with past history of thrombotic complications[2].
Surgical correction of congenital heart diseases Polycythemia can occur secondary to cyanoic congenital heart diseases like tetralogy of fallot and transposition of great arteries as there is poor oxygenation of the blood causing poor tissue perfusion wich ultimately leads to increased eruthropoietin production to compensate the hypoxaemic csituation[6]. Surgical management is the potion for these congenital heart diseases, eg; For tetralogy of fallot, close VSD, relieve right ventricular out flow obstruction and modified Blaock- Taussig shunt will be uhelpful[7]. For transposition of great arteries, balloon atrial septotomy and surgery with arterial switch procedure is needed[8].
Long term oxygen therapy, mucolytics, smoking cessation will useful in COPD patients Chronic pulmonary disease( eg: Chronic Obstructive Pulmonary Disease) can cause progressive ariway obstruction and poor alveolar ventialtion dyspite of good alveolar perfusion. So oygenation of deoxygenated blood in lungs will be poor leading to increased erythropoietin production to compensate the need causing increased red blood cell production. In these patients smoking cessation will be useful in reducing the progression of the disease while Long term oxygen therapy and mucolytics will useful in improving alveolar ventilation[1][9].
There is no specific management for high altitudes causing polycythemia other than changing the residence. In high altitudes there is less oxygen percentage in air compare to other areas. So air coming to alveoli will contain less oxygen causing poor exchange with blood. This induce hypoxic condition to a certain extend causing increase production of erythropoietin to increase the red cell mass which can catch more oxygen and this leads to polycythemia. No treatment will be needed in this condition as this is usually not troublesome[10].
Reduction of obesity by diet control and life style modifications and CPAP ventilation in resistant cases will be helpful in sleep apnoea. In obese people there will be an intermittent closure/ collapse of the pharyngeal air way causing apnoic episodes during sleep. This conditionn leads to periodic alveolar hypoventilation. So periodic hypoxia in long term can induce erythropoietin production causing polycythemia. weight reduction by diet control, life style modifications and with regular physical exercise is needed. CPAP via nasal mask during sleep will be useful. If the condition in intractable surgical procedures can use to relieve the pharyngeal obstruction( eg; tonsillectomy)[5].
Surgical management for renal pathologies like renal tumour and correcting primary cause for hydronephrosis In disease conditions affecting kidneys like renal tumours, hydronephrosis and renal cysts there is associated secondary polycythemia by inappropriate increase in erythropoietin production[4]. Treating these conditions. Renal tumour, radical nephrectomy is the gold stranded treatment[11]. Hydronephrosis can resolve with relieving primary renal/ ureteric obstruction (eg;proximal dilatation for obstruction, removing renal/ureteric stones)[12]. For solitary large cysts, cystectomy will be helpful[13].
Surgical management of hepatocellular carcinoma In hepatocellular carcinoma there is an increased erythropoietin in blood as hepatocellular carcinomal cells leads to erythropoietin production. This stimulates excessive increase production of red blood cells from bone marrows causing polycythemia[14]. In hepatocellular carcinoma resection of solitary tumour, liver transplantation are the main treatment options available[15].
References
  1. TRIPATHY S, PANDA SS, RATH B. Phlebotomy for rapid weaning and extubation in COPD patient with secondary polycythemia and respiratory failure Lung India [online] 2010, 27(1):24-26 [viewed 26 September 2014] Available from: doi:10.4103/0970-2113.59264
  2. BHATT VR. Secondary Polycythemia and the Risk of Venous Thromboembolism J Clin Med Res [online] 2014 Oct, 6(5):395-397 [viewed 26 September 2014] Available from: doi:10.14740/jocmr1916w
  3. MOORE-GILLON J. Smoking--a major cause of polycythemia. J R Soc Med [online] 1988 Jul, 81(7):431 [viewed 26 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1291690
  4. BHAT RA, KHAN I, KHAN I, MIR MA. Polycythemia, increased erythropoietin levels in a patient with renal lymphoma Adv Biomed Res [online] :147 [viewed 26 September 2014] Available from: doi:10.4103/2277-9175.135417
  5. HUKINS CA. Obstructive sleep apnea - management update Neuropsychiatr Dis Treat [online] 2006 Sep, 2(3):309-326 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671821
  6. SOMERVILLE J. GOUT IN CYANOTIC CONGENITAL HEART DISEASE Br Heart J [online] 1961 Jan, 23(1):31-34 [viewed 29 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1017729
  7. WOODSON RD, BURNELL RH, HERR RH, LEES MH, STARR A. Surgical Management of Tetralogy of Fallot in Children under Age Four Ann Surg [online] 1969 Feb, 169(2):257-264 [viewed 29 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1387318
  8. VENUGOPAL P, SUBRAMANIAN S. SURGICAL TREATMENT OF TRANSPOSITION OF THE GREAT ARTERIES WITH INTACT VENTRICULAR SEPTUM UNDER THE AGE OF TWO YEARS Cardiovasc Dis [online] 1974, 1(2):123-126 [viewed 29 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC287474
  9. MACNEE W, CALVERLEY P. Chronic obstructive pulmonary disease o 7: Management of COPD Thorax [online] 2003 Mar, 58(3):261-265 [viewed 29 September 2014] Available from: doi:10.1136/thorax.58.3.261
  10. SCHREIJER AJ, REITSMA PH, CANNEGIETER SC. High hematocrit as a risk factor for venous thrombosis. Cause or innocent bystander? Haematologica [online] 2010 Feb, 95(2):182-184 [viewed 29 September 2014] Available from: doi:10.3324/haematol.2009.017285
  11. CANADIAN KIDNEY CANCER FORUM 2008. Management of kidney cancer: Canadian Kidney Cancer Forum Consensus Statement Can Urol Assoc J [online] 2008 Jun, 2(3):175-182 [viewed 29 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2494902
  12. KWON SY, KIM BS, KIM HT, PARK YK. Efficacy of Percutaneous Nephrostomy During Flexible Ureteroscopy for Renal Stone Management Korean J Urol [online] 2013 Oct, 54(10):689-692 [viewed 29 September 2014] Available from: doi:10.4111/kju.2013.54.10.689
  13. WHELAN TF. Guidelines on the management of renal cyst disease Can Urol Assoc J [online] 2010 Apr, 4(2):98-99 [viewed 29 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845761
  14. SAKISAKA S, WATANABE M, TATEISHI H, HARADA M, SHAKADO S, MIMURA Y, GONDO K, YOSHITAKE M, NOGUCHI K, HINO T. Erythropoietin production in hepatocellular carcinoma cells associated with polycythemia: immunohistochemical evidence. Hepatology [online] 1993 Dec, 18(6):1357-62 [viewed 29 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/7694895
  15. BRUIX J, SHERMAN M. Management of hepatocellular carcinoma: An update Hepatology [online] 2011 Mar, 53(3):1020-1022 [viewed 29 September 2014] Available from: doi:10.1002/hep.24199