The clinical and laboratory findings, in this case, support a diagnosis of polycythaemia vera. A plethoric appearance, lethargy, splenomegaly and itching are common in this disease. Patients may also have gouty arthritis, Budd-Chiari syndrome, erythromelalgia, stroke, myocardial infarction or DVT. The average age for diagnosis of Polycythaemia Vera is 65-74 years. It is a haematological malignancy in which there is overproduction of all three cell lines. Venesection is the treatment of choice as it would cause a decrease in the number of red blood cells within the body.Erythropoietin is given in patients with chronic renal failure as they lack this hormone. Administration of erythropoietin in such patients causes stimulation of the bone marrow to produce red blood cells. Desferrioxamine is a chelating agent for iron and is given to patients with iron overload due to repeated blood transfusions, e.g. in thalassemia patients.Penicillamine is a chelating agent for Copper, given as treatment in Wilson’s disease.

Features include:- severe anaemia (becoming apparent at 3 – 6 months when the switch from gamma-chain to beta-chain production takes place)- failure to thrive- hepatosplenomegaly (due to excessive red cell destruction, extramedullary haemopoiesis and later due to transfusion related iron overload)- expansion of bones (due to marrow hyperplasia, resulting in bossing of the skull and cortical thinning with tendency to fracture)- increased susceptibility to infections (due to anaemia, iron overload, transfusion and splenectomy)- osteoporosis- hyperbilirubinaemia and gallstones- hyperuricaemia and gout- other features of haemolytic anaemia- liver damage and other features of iron overload

Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive disorder in which there is a deficiency of the enzyme G6PD. This causes instability of red blood cell membranes under oxidative stress leading to haemolysis.Triggers include: 1) Fava beans2) Sulphonamides3) Primaquine4) Anti-TB drugs5) Infections Most individuals will be asymptomatic until exposed to one of the triggers listed above. It is the commonest human enzyme defect and affects males more than females because of the X-linked inheritance pattern. The use of penicillins and cephalosporins is generally safe.

Acute haemolytic transfusion reactions present with: Feeling of ‘impending doom’ as the earliest symptom, fever and chills, pain and warmth at transfusion site, nausea and vomiting, back, joint, and chest pain. Transfusion should be stopped immediately and IV fluid (usually normal saline) administered.Supportive measures and paracetamol can be given since patient has fever but it is not the immediate first step.

98% of cases of myeloma occur over the age of 40 years with a peak incidence between 65 and 70 years. The disease is twice as common in black individuals compared to those of white or Asian origin. Laboratory findings include presence of a paraprotein in serum/urine (the paraprotein is IgG in 60% of cases, IgA in 20% and light chain only in almost all the rest) and marked Rouleaux formation on blood film. There is no cure for myeloma. The overall median survival is now 7-10 years and in younger (less than 50 years) patients it can be over 10 years.

Non-Hodgkin’s lymphoma (NHL) refers to a group of lymphoproliferative malignancies (about 85% of B-cell and 15% of T or NK (natural killer) cell origin) with different behavioural patterns and treatment responses. This group of malignancies encompasses all types of lymphoma without Reed-Sternberg cells being present. The Reed-Sternberg cell is classically seen in Hodgkin’s lymphoma.NHL is five times as common as Hodgkin’s lymphoma. The peak incidence of NHL is in the 50-70 years age group, it affects men and women equally, but affects the Caucasian population more commonly than black and Asian ethnic groups.The following are recognised risk factors for NHL:Chromosomal translocations and molecular rearrangementsEpstein-Barr virus infectionHuman T-cell leukaemia virus type-1 (HTLV-1)Hepatitis CCongenital and acquired immunodeficiency statesAutoimmune disorders, e.g. Sjogren’s syndrome and Hashimoto’s thyroiditisThe most common clinical features at presentation are:Lymphadenopathy (typically asymmetrical and painless)Weight lossFatigueNight sweatsHepatosplenomegalyFor clinical purposes, NHL is divided into three groups: indolent, high-grade, and lymphoblastic.Indolent (low-grade) NHL:The cells are relatively matureDisease follows an indolent course without treatmentOften acceptable to follow a ‘watch and wait’ strategyLocal radiotherapy often effectiveRelatively good prognosis with median survival of 10 yearsHigh-grade NHL:Cells are immatureDisease progresses rapidly without treatmentSignificant number of patients can be cured with intensive combination chemotherapy regimensApproximately 40% cure rateLymphoblastic NHL:Cells are very immature and have a propensity to involve the CNSTreatment and progression are similar to that of acute lymphoblastic leukaemia (ALL)

Features may include:Normochromic normocytic anaemia is most common; bone marrow failure involvement is unusual in early disease, but if it occurs bone marrow failure may develop with leucoerythroblastic anaemiaOne-third of patients have a neutrophilia; eosinophilia is frequentAdvanced disease is associated with lymphopenia and loss of cell-mediated immunityPlatelet count is normal or increased in early disease and reduced in later stagesESR and CRP are usually raised (ESR is useful in monitoring disease progress)Serum LDH is raised initially in 30-40% of casesDiagnosis is made by histological examination of an excised lymph nodeThe distinctive multinucleate polypoid RS cell is central to the diagnosis of the four classic types of HL (95% of cases)

The release of cytokines from Reed-Sternberg cells can cause fever in patients with Hodgkin lymphoma, which increases and decreases in a cyclical pattern of 1 to 2 weeks. This is called Pel-Ebstein or Ebstein-Cardarelli fever, specifically seen in Hodgkin lymphoma. The fever is always high grade and can reach 40 degrees or higher.Cyclical fever in other conditions is common but is not termed as Pel-Ebstein fever. This term is reserved only with Hodgkin lymphoma.

Beta-thalassaemia major is caused by a complete or almost complete failure of β-globin chain synthesis, severe imbalance of α:β-chains with deposition of α-chains in erythroblasts, ineffective erythropoiesis and extramedullary haemopoiesis. The severe anaemia becomes apparent at 3 – 6 months when the switch from γ-chain to β-chain synthesis normally occurs. Beta-thalassaemia minor is a variable syndrome, milder than thalassaemia major, with later onset and characterised by moderate hypochromic microcytic anaemia with raised haemoglobin A2. Beta-thalassaemia trait is characterised by mild hypochromic, microcytic anaemia with raised red cell count and raised haemoglobin A2.

Clinical features of haemolytic anaemia include:AnaemiaJaundice (caused by unconjugated bilirubin in plasma, bilirubin is absent from urine)Pigment gallstonesSplenomegalyAnkle ulcersExpansion of marrow with, in children, bone expansion e.g. frontal bossing in beta-thalassaemia majorAplastic crisis caused by parvovirus

Signs and symptoms of Sickle cell disease(SCD):Acute and chronic pain: The most common clinical manifestation of SCD is vaso-occlusive crisis; pain crises are the most distinguishing clinical feature of SCDBone pain: Often seen in long bones of extremities, primarily due to bone marrow infarctionAnaemia: Universally present, chronic, and haemolytic in natureAplastic crisis: Serious complication due to infection with parvovirus B19 (B19V)Splenic sequestration: Characterized by the onset of life-threatening anaemia with rapid enlargement of the spleen and high reticulocyte countInfection: Organisms that pose the greatest danger include encapsulated respiratory bacteria, particularly Streptococcus pneumoniae; adult infections are predominantly with gram-negative organisms, especially SalmonellaGrowth retardation, delayed sexual maturation, being underweightHand-foot syndrome: This is a dactylitis presenting as bilateral painful and swollen hands and/or feet in childrenAcute chest syndrome: Young children present with chest pain, fever, cough, tachypnoea, leucocytosis, and pulmonary infiltrates in the upper lobes; adults are usually afebrile, dyspnoeic with severe chest pain, with multilobar/lower lobe diseasePulmonary hypertension: Increasingly recognized as a serious complication of SCDAvascular necrosis of the femoral or humeral head: Due to vascular occlusionCentral nervous system (CNS) involvement: Most severe manifestation is strokeOphthalmologic involvement: Ptosis, retinal vascular changes, proliferative retinitisCardiac involvement: Dilation of both ventricles and the left atriumGastrointestinal involvement: Cholelithiasis is common in children; liver may become involvedGenitourinary involvement: Kidneys lose concentrating capacity; priapism is a well-recognized complication of SCDDermatologic involvement: Leg ulcers are a chronic painful problem