The most common type of adult leukaemia is chronic lymphocytic leukaemia (CLL). It develops as a result of relatively mature lymphocytes clonally proliferating. The B-cell lineage accounts for approximately 95% of cases. CLL is primarily a disease of adult men, with men over the age of 50 accounting for more than 75% of CLL patients.

It is the most indolent form of chronic leukaemia, and it is frequently discovered by chance when blood counts are taken for other reasons, such as ‘well man’ screening tests. The patient may develop lymphadenopathy, hepatosplenomegaly, anaemia, and infections as the disease progresses.

The following are examples of CLL laboratory findings:
Clonal B cell lymphocytosis (diagnosed at greater than 5 x 109/l, but can reach 300 x 109/l)
In advanced disease, normocytic, normochromic anaemia is present.

Patients with autoimmune-related haemolytic anaemias have a positive direct antiglobulin test (DAT).

Although bone marrow aspiration is not always required, it can aid in the diagnosis of CLL. If there has been rapid lymph node enlargement, a lymph node biopsy is required to rule out Richter’s syndrome. This is the transition from low-grade lymphoma to high-grade lymphoma, which is characterised by fever, weight loss, and pain.

Although there is no cure for CLL, it can be managed with chemotherapy regimens that help patients live longer. Early treatment has no benefit, and the standard treatment for early disease is to watch and wait, with examinations and blood counts every 3 to 12 months. Chemotherapy is usually reserved for patients who have a disease that is active and causing symptoms.

The following is the overall prognosis for CLL:
1/3 will not require treatment and will live a long time.
1/3 will go through an indolent phase before the disease progresses.
1/3 of patients will have an aggressive disease that requires immediate treatment.

Haemophilia B is a bleeding disorder caused by a deficiency of clotting factor IX. It is the second commonest form of haemophilia, and is rarer than haemophilia A. Haemophilia B tends to be similar to haemophilia A but less severe. The two disorders can only be distinguished by specific coagulation factor assays.

The incidence is one-fifth of that of haemophilia A. Laboratory findings demonstrate prolonged APTT, normal PT and low factor IX.
Haemophilia B inherited in an X-linked recessive fashion, affecting males born to carrier mothers.
There is also a variation called Leyden, in which factor IX levels are below 1% until puberty, when they rise, potentially reaching as high as 40-60% of normal. This is thought to be due to the effects of testosterone at puberty.

Haemophilia A is the most common of the hereditary clotting factor deficiencies. The inheritance is sex-linked but up to one-third of patients have no family history and these cases result from recent mutation. The vast majority of cases are inherited in an X-linked recessive fashion, affecting males born to carrier mothers. Females born to affected fathers can also, rarely, be affected due to homozygosity for the gene, where there is marriage to close relatives.

The defect is an absence or low level of plasma factor VIII. The APTT is prolonged but the PT is normal. Recurrent painful haemarthroses and muscle haematomas dominate the clinical course of severely affected patients and if inadequately treated, lead to progressive joint deformity and disability. Local pressure can cause entrapment neuropathy or ischaemic necrosis. Prolonged bleeding occurs after dental extractions or post-trauma. Spontaneous haematuria and gastrointestinal haemorrhage may occur. The clinical severity of the disease correlates inversely with the factor VIII level. Operative and post-traumatic haemorrhage are life-threatening both in severely and mildly affected patients.

Hodgkin’s lymphoma is a malignant tumour of the lymphatic system that is characterised histologically by the presence of Reed-Sternberg cells (multinucleated giant cells). The peak incidence is in young adults aged 20-35, and there is a slight male predominance.

The following are recognised risk factors for Hodgkin’s lymphoma:
Male gender
Age 20-35
Positive family history
Epstein-Barr virus infection
Immunosuppression including HIV infection
Prolonged use of human growth hormone
Most patients present with an enlarged, but otherwise asymptomatic lymph node. The most commonly affected lymph nodes are in the supraclavicular and lower cervical areas. Other common clinical features include shortness of breath and chest discomfort secondary to mediastinal mass. Mediastinal masses are sometimes discovered as incidental findings on routine chest X-rays. Approximately 30% of patients with Hodgkin’s lymphoma develop splenomegaly.
‘B’ symptoms occur in approximately 25% of patients. The ‘B’ symptoms of Hodgkin’s lymphoma are:
Fever (>38ºC)
Night sweats
Weight loss (>10% over 6 months)
Pain after alcohol consumption is a pathognomonic sign of Hodgkin’s lymphoma, it is, however, not a ‘B’ symptom. It is rare though, only occurring in 2-3% of patients with Hodgkin’s lymphoma.

The Ann Arbour clinical staging is as follows:
Stage I: one involved lymph node group
Stage II two involved lymph node groups on one side of the diaphragm
Stage III: lymph node groups involved on both sides of the diaphragm
Stage IV: Involvement of extra-nodal tissues, such as the liver or bone marrow
Diagnosis is made by lymph node biopsy, which should be taken from a sufficiently large specimen or excisional biopsy, as opposed to a fine needle biopsy. The Reed-Sternberg cell is the most useful diagnostic feature. This is a giant cell with twin mirror-image nuclei and prominent ‘owl’s eye’ nucleoli.
The Reed-Sternberg cell of Hodgkin’s Lymphoma
Histological typing depends upon the other cells within the diseased tissue. Nodular sclerosing is the most common type of Hodgkin’s lymphoma. Lymphocyte-depleted and lymphocyte-predominant are rare subtypes.
The majority of cases can be successfully treated, and unlike many other malignancies even if the first-line treatment fails, a cure can often be achieved with second-line therapies. Stage 1 Hodgkin’s lymphoma is usually treated with radiotherapy alone, but more advanced stages require combination chemotherapy. In localised disease treated with irradiation, there is a 5-year survival rate of greater than 80%. In disseminated disease treated with chemotherapy, the 5-year survival falls to around 50%. Overall, a 5-year survival of >70% should be achieved.

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

Laboratory findings typically show (although this varies depending on VWD type):
Abnormal PFA-100 test
Low factor VIII levels (if low a factor VIII/VWF binding assay is performed)
Prolonged APTT (or normal)
Normal PT
Low VWF levels
Defective platelet aggregation
Normal platelet count

Blood loss from the gastrointestinal (GI) tract is the most common cause of iron deficiency anaemia in adult men and postmenopausal women.

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.

Chronic myeloid leukaemia (CML) is a clonal disorder of a pluripotent stem cell. The disease accounts for around 15% of leukaemias and may occur at any age. The diagnosis of CML is rarely difficult and is assisted by the characteristic presence of the Philadelphia (ph) chromosome. This disease occurs in either sex, most frequently between the ages of 40 and 60 years. In up to 50% of cases the diagnosis is made incidentally from a routine blood count. Leucocytosis is the main feature, with a complete spectrum of myeloid cells seen in the peripheral blood. The levels of neutrophils and myelocytes exceed those of blast cells and promyelocytes.Increased circulating basophils are a characteristic feature. Normochromic normocytic anaemia is usual. Platelet count may be increased (most frequently), normal or decreased. The clinical outlook is very good and 90% of patients can expect long-term control of disease.

Immunodeficiency is present in all patients with chronic lymphocytic leukaemia (CLL), though it is often mild and not clinically significant. Infections are the leading cause of death in 25-50 percent of CLL patients, with respiratory tract, skin, and urinary tract infections being the most common.

Hypogammaglobulinemia is the most common cause of immunodeficiency in CLL patients, accounting for about 85 percent of all cases.

Non-Hodgkin’s Lymphoma (NHL) causes neoplastic transformation of both B cell (85%) and T cell (15%) lines.

The most common presentation is with enlarged, rubbery, painless lymph nodes. The patient may also have B symptoms which consist of night sweats, weight loss and fevers. Multiple myeloma most commonly presents with bone pain, especially in the back and ribs.

The presence of Reed-Sternberg cells characterises Hodgkin’s lymphoma. Acute lymphoblastic leukaemia will present with features of anaemia, thrombocytopenia and leukopenia. The most common symptoms of chronic lymphocytic leukaemia are fatigue, night sweats and low-grade fever.

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 rearrangements
Epstein-Barr virus infection
Human T-cell leukaemia virus type-1 (HTLV-1)
Hepatitis C
Congenital and acquired immunodeficiency states
Autoimmune disorders, e.g. Sjogren’s syndrome and Hashimoto’s thyroiditis

Chronic myeloid leukaemia is most common in middle-aged and elderly people. It is responsible for 20% of all leukemias. The majority of CML patients experience fatigue, weight loss, and excessive sweating.

The Philadelphia chromosome is found in over 90% of CML cases. A balanced translocation between chromosomes 9 and 22 is known as the Philadelphia chromosome.

Because white cells produce a B12 binding protein, serum B12 levels in CML are typically high.

In CML, the neutrophil alkaline phosphatase score is usually low.

Almost all patients with CML eventually progress to blast crisis, though this can take up to ten years. If any of the following features are present in a CML patient, a blast crisis is diagnosed:
In the blood or bone marrow, there are more than 20% myeloblasts or lymphoblasts.
On a bone marrow biopsy, large clusters of blasts were discovered.

CML can be treated with tyrosine kinase inhibitors like imatinib and dasatinib if a chloroma (a solid tumour made up of myeloblasts that grows outside of the bone marrow) is present.

Deficiency of Factor IX causes Haemophilia B, and like the other Haemophilia’s, it has an X-linked recessive pattern of inheritance, affecting males born to carrier mothers.

Haemophilia B is the second commonest form of haemophilia and is rarer than haemophilia A. Haemophilia B is similar to haemophilia A but is less severe. You can distinguish the two disorders by specific coagulation factor assays.

The incidence of Haemophilia B is one-fifth of that of haemophilia A.

In laboratory findings, you get prolonged APTT, normal PT and low factor IX for Haemophilia B.

There is also a variation called Leyden, in which factor IX levels are below 1% until puberty, when they rise, potentially reaching as high as 40-60% of normal. This is thought to be due to the effects of testosterone at puberty.

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.

Megaloblastic anaemia occurs when there is inhibition of DNA synthesis as red blood cells are produced. Impairment of DNA synthesis causes the cell cycle to be unable to progress from the growth stage to the mitosis stage. As a result, there is continuous cell growth without division, with an increase in mean corpuscular volume (MCV), which presents as macrocytosis. The most common cause of this defect in red cell DNA synthesis is hypovitaminosis, in particular, vitamin B12 deficiency or folate deficiency.
Folate is an essential vitamin that can be found in most foods, and is highest in liver, green vegetables and yeast. 200 – 250 μg is found in the normal daily diet, and about 50% is absorbed. The daily adult requirement is about 100 μg and its absorption is principally from the duodenum and jejunum. Folate stores are normally only adequate for 4 months and so clinical features of folate deficiency usually become evident after this time.

Causes of intravascular haemolysis:
Haemolytic transfusion reactions
G6PD deficiency
Red cell fragmentation syndromes
Some severe autoimmune haemolytic anaemias
Some drug-and infection-induced haemolytic anaemias
Paroxysmal nocturnal haemoglobinuria

Hand-foot syndrome in children is typically the first symptom of the disease, produced by infarction of the metaphysis of small bones. The disease is inherited as an autosomal recessive trait. By adulthood, the spleen has usually infarcted. Infection with the B19 parvovirus is usually followed by an aplastic crisis. Thrombocytopenia is caused by splenic sequestration.

Abciximab, eptifibatide and tirofiban are GPIIb/IIIa inhibitors, inhibiting platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor and other adhesive molecules.

Approximately one-third of patients who suffer DVT or PE have an identifiable heritable risk factor, although additional risk factors are usually present when they develop the thrombosis. The history of a spontaneous DVT in a close relative increases an individual’s risk of DVT even if no known genetic predisposition can be identified.

A serious complication in sickle cell disease (SCD) is the aplastic crisis. This may be caused by infection with Parvovirus B-19 (B19V). This virus causes fifth disease, a normally benign childhood disorder associated with fever, malaise, and a mild rash. This virus infects RBC progenitors in bone marrow, resulting in impaired cell division for a few days.
Healthy people experience, at most, a slight drop in hematocrit, since the half-life of normal erythrocytes in the circulation is 40-60 days. In people with SCD, however, the RBC lifespan is greatly shortened (usually 10-20 days), and a very rapid drop in Hb occurs. The condition is self-limited, with bone marrow recovery occurring in 7-10 days, followed by brisk reticulocytosis.