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

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

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.

ALL affects children predominantly.The CNS is commonly involved in ALL.The Philadelphia chromosome is present in 25% of adult ALL and 5% of childhood ALL cases.The cure rate in children is approximately 80% in children and 50% in adults.ALL is classified into 3 groups using the French-American-British (FAB) classification:ALL-L1: small uniform cellsALL-L2: large varied cellsALL-L3: large varied cells with vacuoles.

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 groupStage II two involved lymph node groups on one side of the diaphragmStage III: lymph node groups involved on both sides of the diaphragmStage IV: Involvement of extra-nodal tissues, such as the liver or bone marrowDiagnosis 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.

Fat-soluble vitamin K is obtained from green vegetables and bacterial synthesis in the gut. Deficiency may present in the newborn (haemorrhagic disease of the newborn) or in later life. Deficiency may be caused by an inadequate diet, malabsorption or inhibition of vitamin K by drugs such as warfarin. The activity of factors II, VII, IX and X are vitamin K dependent as well as that of protein C and protein S. Both PT and APTT are prolonged.

Anaemia is defined as a reduction in haemoglobin concentration below the normal range for the age and sex of the individual. Children tend to have lower haemoglobin than adults, and women tend to have lower haemoglobin than men. Anaemia may occur from an actual reduction in total circulating haemoglobin mass, or with an increase in plasma volume e.g. in pregnancy, causing a dilutional anaemia. After acute major blood loss, anaemia is not immediately apparent because total blood volume is reduced and it takes up to a day for plasma volume to be replaced and hence the degree of anaemia to become apparent. The initial clinical features in acute haemorrhage are therefore a result of reduction in blood volume rather than that of anaemia. When anaemia develops slowly, the associated symptoms are often very mild as the body has time to adapt to the fall in haemoglobin. This involves mechanisms such as an increase in red cell 2,3 -diphosphoglycerate (2,3 – DPG), which shifts the oxygen dissociation curve to the right, allowing enhanced delivery of O2 to the tissues, and an increase in stroke volume and heart rate.

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. Typical 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.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. TRALI (Transfusion Related Acute Lung Injury) is a clinical syndrome with abrupt onset of non-cardiogenic pulmonary oedema within 6 hours of transfusion not explained by another risk factor. Associated with the presence of antibodies in the donor blood to recipient leukocyte antigens. patients present with dyspnoea, hypertension, hypotension, acute leukopenia. 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.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.

Features of intravascular haemolysis include:haemoglobinaemia, methaemalbuminaemia, haemoglobinuria (dark urine) and haemosiderinuria

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.

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults and becomes increasingly common with age, with a median onset of 65 years. It forms only a minor fraction (10 – 15%) of childhood leukaemia. The clinical features of AML typically presents with clinical features secondary to leukaemic infiltration of bone marrow and extramedullary sites: Anaemia (lethargy, pallor and breathlessness)Thrombocytopaenia (petechiae, bruising, epistaxis, haemorrhage) – often profoundNeutropenia (infections)HepatosplenomegalyGingival infiltrationCentral nervous system involvement in AML is uncommon.Leukaemia cutis is the infiltration of neoplastic leukocytes in the skin. It occurs in approximately 10% of patients with AML.Haematological investigations reveal a normochromic normocytic anaemia with thrombocytopenia in most cases. The total white cell count is usually increased and blood film examination typically shows a variable number of blast cells. The bone marrow is hypercellular and typically contains many blast cells.. The prognosis for patients with AML has been improving steadily, particularly for those under 60 years of age, and approximately one-third of patients of this group can expect to achieve long-term cure. For the elderly, the situation is poor and less than 10% of those over 70 years of age achieve long-term remission.CML is commonly associated with the Philadelphia chromosome. The Philadelphia chromosome is present in only 1% of adults AML cases.Lymphadenopathy is rare in AML.

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.

Factor V Leiden gene mutation is the most common inherited cause of an increased risk of venous thrombosis. Activated protein C normally breaks down activated factor V and so should slow the clotting reaction and prolong the APTT, but a mutation in the factor V gene makes factor V less susceptible to cleavage by activated protein C, resulting in increased levels of activated factor V.Heterozygotes for factor V Leiden are at an approximately five- to eight- fold increased risk of venous thrombosis compared to the general population (but only 10% of carriers will develop thrombosis in their lifetime). Homozygotes have a 30 – 140-fold increased risk. The incidence of factor V Leiden in patients with venous thrombosis is approximately 20 – 40%. It does not increase the risk of arterial thrombosis.

Non-specific signs of anaemia include: 1. pallor of mucous membranes or nail beds (if Hb < 90 g/L), 2. tachycardia3. bounding pulse4. wide pulse pressure5. flow murmurs 6. cardiomegaly 7. signs of congestive cardiac failure (in severe cases)

Multiple myeloma is a clonal abnormality affecting plasma cells in which there is an overproduction of functionless immunoglobulins. The most common patient complaint is bone pain, especially in the back and ribs. Anaemia and renal failure are common, along with hypercalcemia. Hypercalcemia may lead to an altered mental status, as in this case. Chronic lymphocytic leukaemia occurs due to the overproduction of lymphocytes, usually B cells. CLL may present with an asymptomatic elevation of B cells. Patients are generally more than 50 years old and present with non-specific fatigue and weight loss symptoms.There is no history of alcohol abuse in this case. Furthermore, patients with a history of alcohol abuse may have signs of liver failure, which are not present here. Metastatic prostate cancer would most often cause lower backache as it metastasises first to the lumbar spine via the vertebral venous plexus. A patient with Vitamin B12 deficiency would have anaemia, megaloblastic, hypersegmented neutrophils, and signs of peripheral neuropathy.

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.

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 exhaustionNight sweats and feverDistension of the abdomenPain in the left upper quadrant (splenic infarction)Splenomegaly (commonest examination finding)HepatomegalyBruising 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.

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.

Dietary iron may be in the form of haem or non-haem iron. Haem iron is degraded after absorption through the cell surface to release Fe2+. Most non-haem iron is in the form Fe3+, which is reduced at the luminal surface to the more soluble Fe2+, facilitated by hydrochloric acid in gastric secretions (and enhanced by ascorbic acid). Fe2+is taken across the enterocyte apical membrane by the divalent metal transporter (DMT1). In the enterocyte, Fe2+is then either stored in enterocyte epithelial cells as ferritin, or released into portal plasma via the molecule ferroportin at the basolateral membrane.

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.

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

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

Lymphoma is a cancer of the lymphatic system, which is part of the body’s germ-fighting network. They are a group of diseases that are caused by malignant lymphocytes. These malignant cells accumulate in lymph nodes and other lymphoid tissue, giving rise to the characteristic clinical feature of lymphadenopathy. They can be subdivided into Hodgkin lymphoma (HL) which are characterised by the presence of Reed-Sternberg cells, and non-Hodgkin lymphoma (NHL). Characteristics of HL include:1. can present at any age but is rare in children and has a peak incidence in young adults, 2. almost 2:1 male predominance. 3. presents with painless, asymmetrical, firm and discrete enlargement of superficial lymph nodes. 4. cervical node involvement in 60-70% of cases, 5. axillary node involvement in 10-15% 6. inguinal node involvement in 6-12%. 7. modest splenomegaly during the course of the disease in 50% of patients8. may occasionally have liver enlargement9. bone marrow failure involvement is unusual in early disease. Approximately 85% of patients are cured, but the prognosis depends on age, stage and histology. Two well‐known but rare symptoms in HL are alcohol‐induced pain and pruritus.

Laboratory results often show that:PFA-100 test results are abnormal.Low levels of factor VIII (if a factor VIII/VWF binding assay is conducted)APTT is Prolonged (or normal)PT is normalVWF values are low.Defective Platelet aggregationThe platelet count is normal.

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

Chronic ITP is a relatively common disorder. The highest incidence is in women aged 15 – 50 years. It is the most common cause of thrombocytopaenia without anaemia or neutropaenia. It is usually idiopathic but it may been seen in association with other conditions. Platelet autoantibodies (usually IgG) result in the premature removal of platelets from the circulation by macrophages of the reticuloendothelial system. In many causes the antibody is directed against the glycoprotein IIb/IIIa or Ib complex. The normal platelet lifespan of 10 days is reduced to a few hours. Total megakaryocyte mass and platelet turnover are increased to approximately five times normal. Despite the destruction of platelets by splenic macrophages, the spleen is normally not enlarged.  In fact, an enlarged spleen should lead to a search for other possible causes for the thrombocytopenia.

Blood transfusion can be a life-saving treatment with significant clinical benefits, but it also comes with a number of risks and potential complications, including:Immunological side effectsErrors in administration (episodes of ‘wrong blood’)Viruses and Infections (bacterial, viral, possibly prion)ImmunodilutionA culture of better safety procedures as well as steps to reduce the use of transfusion has emerged as a result of growing awareness of avoidable risk and improved reporting systems. Transfusion errors, on the other hand, continue to occur, and some serious adverse reactions go unreported.Transfusion-associated graft-vs-host disease (TA-GVHD) is a rare blood transfusion complication that causes fever, rash, and diarrhoea 1-4 weeks after the transfusion. Pancytopenia and liver function abnormalities are common laboratory findings.TA-GVHD, unlike GVHD following allogeneic marrow transplantation, causes profound marrow aplasia with a mortality rate of >90%. Survival is uncommon, with death occurring within 1-3 weeks of the onset of symptoms.Because of immunodeficiency, severe immunosuppression, or shared HLA antigens, viable T lymphocytes in blood components are transfused, engraft, and react against the recipient’s tissues, and the recipient is unable to reject the donor lymphocytes.The following is a list of the most common transfusion reactions and complications:1) Reaction to a febrile transfusionThe temperature rises by one degree from the baseline. Chills and malaise are also possible symptoms.The most common response (1 in 8 transfusions).Cytokines from leukocytes in transfused red cell or platelet components are usually to blame.Only supportive. The use of paracetamol is beneficial.2) Acute haemolytic reaction is a type of haemolytic reaction that occurs when theFever, chills, pain at the transfusion site, nausea, vomiting, and dark urine are all symptoms of a transfusion reaction.Early on, many people report a sense of ‘impending doom.’The most serious reaction. ABO incompatibility is frequently caused by a clerical error.STOP THE TRANSFUSION OF INFORMATION. IV fluids should be given. It’s possible that diuretics will be required.3) Haemolytic reaction that is delayedIt usually happens 4 to 8 days after a blood transfusion.Fever, anaemia, jaundice, and haemoglobinuria are all symptoms that the patient has.Positive Coombs test for direct antiglobulin.Because of the low titre antibody, it is difficult to detect in a cross-match, and it is unable to cause lysis at the time of transfusion.The majority of delayed haemolytic reactions are harmless and do not require treatment.Anaemia and renal function should be monitored and treated as needed.4) Reaction to allergensForeign plasma proteins are usually to blame, but anti-IgA could also be to blame.Urticaria, pruritus, and hives are typical allergic reactions. It’s possible that it’s linked to laryngeal oedema or bronchospasm.Anaphylaxis is a rare occurrence.Antihistamines can be used to treat allergic reactions symptomatically. It is not necessary to stop transfusions.If the patient develops anaphylaxis, the transfusion should be stopped and the patient should be given adrenaline and treated according to the ALS protocol.5) TRALI (Transfusion Related Acute Lung Injury)Within 6 hours of transfusion, there was a sudden onset of non-cardiogenic pulmonary oedema.It’s linked to the presence of antibodies to recipient leukocyte antigens in the donor blood.The most common cause of death from transfusion reactions is this.STOP THE TRANSFUSION OF INFORMATION. Oxygen should be given to the patient. Around 75% of patients will require aggressive respiratory support.The use of diuretics should be avoided.6) TACO (Transfusion Associated Circulatory Overload)Acute or worsening respiratory distress within 6 hours of a large blood transfusion. Fluid overload and pulmonary and peripheral oedema can be seen. Rapid blood pressure rises are common. BNP is usually 1.5 times higher than it was before the transfusion. It is most common in the elderly and those who have chronic anaemia.Blood transfusions should be given slowly, over the course of 3-4 hours.

Glanzmann’s thromboasthenia is a rare platelet disorder in which platelets contain defective or low levels of glycoprotein IIb/IIIa.

The history of nosebleeds and fatigue, and gingival hyperplasia presents a typical picture of acute myeloid leukaemia. Leukemic infiltrates within the gingiva cause hypertrophy and distinguish this condition from other types of leukaemia. The fatigue is secondary to anaemia, while the nosebleeds are caused by thrombocytopenia secondary to leukemic infiltration of bone marrow. Patients may also report frequent infections secondary to neutropenia and hepatosplenomegaly.

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.