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

Acute lymphoblastic leukaemia (ALL) is a clonal (malignant) bone marrow disorder in which early lymphoid precursors multiply and replace the marrow’s normal hematopoietic cells. ALL is most common between the ages of 3 and 7, with 75 percent of cases occurring before the age of 6.

Neutropenia is defined as a total neutrophil count of < 2.0 x 109/l.
It can be caused by:
Viral infections
Collagen disease e.g. SLE and RA
Chemotherapy and radiotherapy
Hypersplenism
Marrow infiltration
Vitamin and folate deficiency
Drug reactions
Drugs that cause neutropenia include flecainide, phenytoin, carbimazole, indomethacin and co-trimoxazole.

Anaemia of chronic disease is one of the most common causes of normocytic anaemia. The anaemia is usually mild (Hb > 90 g/L) and non-progressive. Anaemia of chronic disease is usually associated with low serum iron, low transferrin saturation, and a low total iron binding capacity (TIBC) with normal or raised ferritin which differentiates it from iron deficiency anaemia.

Dipyridamole inhibits both the reuptake of adenosine and phosphodiesterase, preventing the degradation of cAMP and thus blocking the platelet aggregation response to ADP.

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.

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.

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.

A history of stroke and poor nutritional status points towards a nutritional deficiency as the most likely cause of her symptoms. The examination would differentiate between Vitamin B12 and Folic acid deficiency as in the former. The patient has a beefy red tongue and symptoms indicating peripheral nervous system involvement or subacute combined spinal cord degeneration. The patient may also have a lemon-yellow skin colour, loss of proprioception and vibratory sense and oral ulceration.

Investigations in B12 deficiency can reveal the following:
1. Macrocytic anaemia
2. Neutropoenia
3. Thrombocytopaenia
4. Blood film: anisocytosis, poikilocytosis
5. Low serum B12
6. Raised serum bilirubin (haemolysis)
7. Intrinsic factor antibodies
8. Positive Schilling test

The collection of abnormalities found in these patients is referred to as a hyposplenic film.
The following features can be seen on hyposplenic blood films:
Howell-Jolly bodies
Heinz’s bodies
Target cells
RBCs with nuclei on occasion
Lymphocytosis
Macrocytosis
Acanthocytes
Teardrop cells, also known as dacrocytes, are named for their teardrop-shaped shape.

Dacrocytosis is a condition in which a large number of these cells are present. Myelofibrosis and beta thalassemia major both have dacrocytes, but hyposplenism does not.

Lymphomas are a group of diseases caused by malignant lymphocytes that accumulate in lymph nodes and other lymphoid tissue and cause the characteristic clinical feature of lymphadenopathy. The major subdivision of lymphomas is into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) and this is based on the histological presence of Reed-Sternberg cells present in HL. Hodgkin lymphoma can present at any age but is rare in children and has a peak incidence in young adults. There is an almost 2 : 1 male predominance. Most patients present with painless, asymmetrical, firm and discrete enlargement of superficial lymph nodes. Cervical nodes are involved in 60-70% of cases, axillary nodes in 10-15% and inguinal nodes in 6-12%. Modest splenomegaly occurs during the course of the disease in 50% of patients; the liver may also be enlarged. Bone marrow failure involvement is unusual in early disease. The prognosis depends on age, stage and histology, but overall approximately 85% of patients are cured. Alcohol‐induced pain and pruritus are two well‐known but rare symptoms in HL.

The presence of Reed-Sternberg cells is pathognomonic for Hodgkin’s Lymphoma, which is a disease-causing neoplastic transformation of lymphocytes. There is a bimodal age distribution with peaks in the 20s and 60s. Patients typically present with enlarged, rubbery, non-tender lymph nodes. Symptoms such as fever, night sweats and weight loss may be present.

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.

Multiple myeloma most commonly presents with bone pain, especially in the back and ribs.

In non-Hodgkin’s lymphoma, Reed-Sternberg cells are not present.

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.

Acute lymphoblastic leukaemia (ALL) is the most common childhood cancer that primarily affects children. ALL is most common between the ages of 2 and 4, and it is uncommon in adults.

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 SCD
Bone pain: Often seen in long bones of extremities, primarily due to bone marrow infarction
Anaemia: Universally present, chronic, and haemolytic in nature
Aplastic 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 count
Infection: Organisms that pose the greatest danger include encapsulated respiratory bacteria, particularly Streptococcus pneumoniae; adult infections are predominantly with gram-negative organisms, especially Salmonella
Growth retardation, delayed sexual maturation, being underweight
Hand-foot syndrome: This is a dactylitis presenting as bilateral painful and swollen hands and/or feet in children
Acute 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 disease
Pulmonary hypertension: Increasingly recognized as a serious complication of SCD
Avascular necrosis of the femoral or humeral head: Due to vascular occlusion
Central nervous system (CNS) involvement: Most severe manifestation is stroke
Ophthalmologic involvement: Ptosis, retinal vascular changes, proliferative retinitis
Cardiac involvement: Dilation of both ventricles and the left atrium
Gastrointestinal involvement: Cholelithiasis is common in children; liver may become involved
Genitourinary involvement: Kidneys lose concentrating capacity; priapism is a well-recognized complication of SCD
Dermatologic involvement: Leg ulcers are a chronic painful problem

Anaphylaxis transfusion reaction occurs when an individual has previously been sensitized to an allergen present in the blood and, on re-exposure, releases IgE or IgG antibodies. Patients with anaphylaxis usually develop laryngospasm, bronchospasm, abdominal pain, nausea, vomiting, hypotension, shock, and loss of consciousness. The transfusion should be stopped immediately and the patient should be treated with adrenaline, oxygen, corticosteroids, and antihistamines.

Aplastic anaemia is a life-threatening failure of haemopoiesis characterised by pancytopenia and hypocellular bone marrow. It is rare and patients present with features of recurrent infections secondary to (leukocytopenia), increased bleeding tendency (secondary to thrombocytopenia) and anaemia. In aplastic anaemia, there is damage to the bone marrow and the haematopoietic stems cells leading to pancytopenia.

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

CML is a myeloproliferative disorder characterised by an abnormal pluripotent haemopoietic stem cell. A cytogenetic abnormality known as the Philadelphia chromosome, which results from a reciprocal translocation between the long arms of chromosomes 9 and 22, causes more than 80% of cases of CML.

CML is a disease that develops slowly over several years. This is known as the ‘chronic stage.’ This stage is usually asymptomatic, and 90 percent of patients are diagnosed at this point, with the disease being discovered frequently as a result of a routine blood test. During this stage, the bone marrow contains less than 10% immature white cells (blasts).

When CML cells expand, symptoms typically begin to appear. The ‘accelerated stage’ is what it’s called. Approximately 10% of people are diagnosed at this point. During this stage, between 10% and 30% of blood cells in the bone marrow are blasts. During this stage, common clinical features include:
Fatigue and exhaustion
Night sweats and fever
Distension of the abdomen
Pain in the left upper quadrant (splenic infarction)
Splenomegaly (commonest examination finding)
Hepatomegaly
Bruising is simple.
Gout is a type of arthritis that affects (rapid cell turnover)
Hyperviscosity is a condition in which the viscosity of (CVA, priapism)
A small percentage of patients experience a ‘blast crisis’ (blast stage). More than 30% of the blood cells in the bone marrow are immature blast cells at this stage. Patients with severe constitutional symptoms (fever, weight loss, bone pain), infections, and bleeding diathesis typically present at this stage.

In CML, laboratory findings include:
White cell count is abnormally high (often greater than 100 x 109/l).
Increased number of immature leukocytes causes a left shift.
Anaemia that is mild to moderately normochromic and normocytic.
Platelets can be low, normal, or elevated, and the Philadelphia chromosome can be found in > 80% of patients.
Serum uric acid and ALP levels are frequently elevated.
Tyrosine kinase inhibitors (TKIs), such as imatinib and dasatinib, are the current mainstay of CML treatment.
Allogenic bone marrow transplantation is now only used in cases where TKIs have failed to work.

Febrile transfusion reactions presents with an unexpected temperature rise (≥ 38ºC or ≥ 1ºC above baseline, if baseline ≥ 37ºC) during or shortly after transfusion. It is usually an isolated finding and the fever is accompanied by chills and malaise occasionally.

Allergic reaction is commonly caused by foreign plasma proteins but may be due to anti-IgA. Allergic type reactions usually present with urticaria, pruritus, hives. Associations include laryngeal oedema or bronchospasm.

Acute haemolytic reaction aka immediate haemolytic transfusion reaction presents with fever, chills, pain at transfusion site, nausea, vomiting, dark urine and feeling of ‘impending doom’. Often, it occurs due to ABO incompatibility.

Transfusion-associated circulatory overload (TACO) presents as acute or worsening respiratory distress within 6 hours of transfusion of a large volume of blood. It is common in patients with diminished cardiac reserve or chronic anaemia. Elderly patients, infants and severely anaemic patients are particularly susceptible. Clinical features of TACO include: Acute respiratory distress, Tachycardia, Hypertension, Acute/worsening pulmonary oedema on chest X-ray. The BNP is usually raised to at least 1.5 times the pre-transfusion baseline.

Transfusion-related lung injury (TRALI) is a form of acute respiratory distress caused by the donor plasma containing antibodies against the patient’s leukocytes. It is defined as hypoxia and bilateral pulmonary oedema that occurs within 6 hours of a transfusion in the absence of other causes of acute lung injury. Clinical features include Breathlessness, cough, frothy sputum, hypertension or hypotension, hypoxia and fever. Chest X-ray shows multiple perihilar nodules with infiltration of the lower lung fields.

Delayed haemolytic transfusion reactions (DHTRs) commonly occurs 4-8 days after blood transfusion, but can occur up to a month after. Signs and symptoms include jaundice, fever, an inadequate rise in PCV, reticulocytosis, a positive antibody screen and a positive Direct Antiglobulin Test (Coombs test). DHTRs usually have a benign course and require no treatment but sometimes, life-threatening haemolysis with severe anaemia and renal failure can occur so haemoglobin levels and renal function should be monitored.

Acute haemolytic reaction aka immediate haemolytic transfusion reaction presents with fever, chills, pain at transfusion site, nausea, vomiting, dark urine and feeling of ‘impending doom’. Often, it occurs due to ABO incompatibility.

Febrile transfusion reaction presents with a 1 degree rise in temperature from baseline during transfusion. Patient may have chills and malaise. It is the most common transfusion reaction (1 in 8 transfusions) and is usually caused by cytokines released from leukocytes in transfused red cell or platelet components.

Transfusion-associated circulatory overload (TACO) presents as acute or worsening respiratory distress within 6 hours of transfusion of a large volume of blood. It is common in patients with diminished cardiac reserve or chronic anaemia. Elderly patients, infants and severely anaemic patients are particularly susceptible. Clinical features of TACO include: Acute respiratory distress, Tachycardia, Hypertension, Acute/worsening pulmonary oedema on chest X-ray. The BNP is usually raised to at least 1.5 times the pre-transfusion baseline.

Graft versus host disease(GVHD) is an immune mediated condition that arises from a complex interaction between donor and recipients adaptive immunity. It presents as dermatitis, hepatitis and enteritis developing within 100 days after stem cell or bone marrow transplant.