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Flashcards in Haematology Deck (53)
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Haemostasis disorders: Thrombocytopaenia

This may be due to a failure of platelet production or increased destruction or sequestration of platelets, and abnormal platelet function.

Abnormal platelet function may cause bleeding despite a normal platelet count. Abnormal platelet function may occur with: drugs, e.g. aspirin, non-steroidal anti- inflammatory drugs, carbenicillin, and ticarcillin; uraemia; septicaemia; and von Willebrand’s disease.


Haemostasis disorders: Blood vessel wall abnormalities

Blood vessel wall abnormalities
These are rare and may be due to scurvy, steroids, Cushing’s syndrome, or Henoch-Schonlein purpura.


Haemophilia A

These are uncommon, the commonest being haemophilia A and von Willebrand’s disease.

Haemophilia A This is due to an inherited deficiency of Factor VIII. It is an X-linked recessive disorder affecting males and carried by females. Severity of the disease depends on the degree of factor VIII deficiency. The PT is normal but the APTT is prolonged.


von Willebrand’s disease

This is due to deficiency of von Willebrand’s factor. It is transmitted as an autosomal dominant condition. Vascular endothelium releases decreased amounts of factor VIII. Although the platelet count is usually normal, platelet inter- action with the endothelium is defective because of deficiency of von Willebrand’s factor.


Vitamin K deficiency

Vitamin K is present in green vegetables and is synthesised by intestinal bacteria. It is fat soluble and requires bile for its absorption. It is required for the formation of factors II, VII, IX, X. Vitamin K deficiency may occur in the surgical patient as the result of obstructive jaundice, antibiotic therapy which alters the normal intestinal flora, or prolonged parenteral nutrition without vitamin K supplements.


Coagulation disorder: Liver disease

This is commonly associated with coagulation defects due to failure of clotting factor synthesis and the production of abnormal fibrinogen. Vitamin K will not help if there is hepatocellular fail- ure. In addition, there may be thrombocytopaenia due to hypersplenism.


Disseminated intravascular coagulation (DIC)

This results from simultaneous activation of coagulation and fibrinolytic systems. Activation of the coagulation system leads to the formation of microthrombi in many organs, with the consumption of clotting factors and platelets, in turn leading to haemorrhage. DIC may arise as a result of the following disorders: septicaemia, malignancy, trauma, shock, liver disease, acute pancrea- titis, obstetric problems, e.g. toxaemia, amniotic fluid embolism. Clinically there is widespread haemorrhage. The presence of thrombocytopaenia, decreased fibrino- gen, and elevated fibrinogen degradation products con- firms the diagnosis.


Natural anticoagulants: Antithrombin III

This is an inhibitor of thrombin, its action being potentiated by heparin. Congenital antithrombin III deficiency is inherited as an autosomal dominant. Heterozygotes may suffer from recurrent DVT, pulmonary embolism, and mesenteric thrombosis. Homozygotes present in childhood with severe arterial and venous thrombosis.


Natural anticoagulants: Protein C and protein S

These are synthesised in the liver and are dependant on vitamin K. Protein C degrades factors Va and VIIIa and promotes fibrinolysis by inactivating plasminogen-activator inhibitor I.

Protein S is a cofactor for protein C and enhances its activity. Hereditary protein C deficiency may occur, patients being more susceptible to DVT, PE, superficial thrombophlebitis, and cerebral venous thrombosis.


Anticoagulant drugs: Heparin

Heparin potentiates the action of antithrombin III. Standard unfractionated heparin is administered i.v. or s.c. and has a half life of about 1h. Low molecular weight heparin is used subcutaneously and has a longer biological half life. Intravenous heparin is used in patients with DVT or PE, and the dosage is monitored by performing the KCCT, which should be maintained at 2–2.5 times the normal value.

Subcutaneous heparin is given to reduce the risk of DVT or PE in patients undergoing major surgery or patients who are on prolonged bed rest, e.g. post-myocardial infarction or orthopaedic patients. Heparin does not cross the placenta and is, therefore, the drug of choice when anticoagulation is required during pregnancy. Bleeding due to overdose is managed by stopping the heparin and administering protamine sulphate intravenously. Side effects of heparin include thrombocytopaenia, hypersensitivity reactions, alopecia, and osteoporosis when used long term.



Warfarin is a coumarin derivative which is administered orally. It is a vitamin K antagonist and in effect induces a state analogous to vitamin K deficiency. It interferes with the activity of factors II, VII, IX and X. It delays thrombin generation, thus preventing the formation of thrombi. It is usual to give a loading dose (10 mg) and to determine the INR (the prothrombin ratio standardised by correcting for the sensitivity of the thromboplastin used) about 15–18 h later. Subsequent doses are based on the INR.

Warfarin is usually administered for 3–6 months following DVT or PE. Lifelong warfarin is required for recurrent venous thromboembolic disease, some prosthetic heart valves, congenital deficiency of antithrombin III, deficiency of protein C or protein S,
patients with lupus anticoagulant, and valvular heart disease complicated by embolism or atrial fibrillation.

Bleeding is controlled by stopping warfarin and administering either fresh frozen plasma or vitamin K, depending upon the degree of urgency. If vitamin K is used there is a period of resistance to warfarin, and control may be difficult initially when the patient is restarted on warfarin. A number of drugs may interfere with the control of warfarin. These include antibiotics, laxatives (interfere with vitamin K absorption), phenylbutazone (interferes with binding of warfarin to albumin) and cimetidine (inhibits hepatic microsomal degradation). Warfarin crosses the placenta and is teratogenic. It should be avoided particularly in the first trimester of pregnancy.


Transfusion: Whole blood

Nowadays whole blood is less readily available because of the demand for blood products. Most blood for transfusion is essentially red cells alone. Ideally, whole blood should be the product of choice for massive transfusion but in practice concentrated red cells with colloid or crystalloid is given usually following massive haemorrhage. Whole blood may be stored for up to 42 days. Granulocytes and platelets lose their function in a few days and clotting factors V and VIII are rapidly lost. In stored blood there is an increasing content of lactate, phosphate and potassium but this is usually clinically insignificant, except when massive blood transfusions are administered.


Transfusion: Red cell concentrates

Red cell concentrates, or packed cells, consist of whole blood from which the majority of plasma has been removed. This type of blood is the treatment of choice for anaemia without hypovolaemia. The shelf life of red cell concentrates is 42 days at 4C. However, during storage changes take place in the constituents of the blood. These are as follows:

• increased lactate;
• increased potassium;
• increased phosphate;
• decrease in pH;
• haemolysis
• microaggregation of dead cells
• loss of granulocyte and platelet function
• loss of factor V and factor VIII


Transfusion: Platelet concentrates

Platelet concentrates consist of platelets suspended in plasma. Their shelf-life is only three days at room temperature. The transfusion should be ABO compatible. Indications for platelet transfusion include:

• haemorrhage in the presence of thrombocytopenia
• thrombocytopenia prior to an invasive
• consumptive coagulopathy, e.g. DIC; and
• platelet counts of 50,000  109/L are adequate for

Administration of platelet concentrate should occur four hours before any invasive procedure. Transfusion should be rapid via a short giving set with no filter. The usual adult dose is six units which should raise the platelet count by 40,000  109/L. Counts should be checked 10 mins to one hour post-transfusion. Failure of the count to rise may be due to platelet antibodies, post-transfusion purpura or DIC.


Transfusion: Granulocytes

Granulocytes have a very short shelf-life (24 h at room temperature). Granulocyte transfusions are expensive. The effect of infusion is short-lived and often induces a pyrexial response. The role of granulocyte infusions remains controversial. Granulocyte-colony stimulat- ing factor (G-CSF) is now used to stimulate a bone marrow response.


Transfusion: Fresh frozen plasma

Fresh frozen plasma (FFP) is plasma which is separated from fresh blood and frozen at 30C. It contains all the clotting factors. Shelf-life of FFP is one year at 30C. FFP should be used within one hour of thawing.

Indications for the use of FFP include:
• to replace clotting factors following major haemorrhage (due to poor clotting ability of stored blood);
• patients short of clotting factors (e.g. liver disease or for the rapid reversal of warfarin)
• DIC, when it should be given in conjunction with platelets and cryoprecipitate; and
• prophylaxis or treatment of haemorrhage in patients with specific clotting defects for which the specific factor is unavailable. Group compatible FFP should be used.


Transfusion: Cryoprecipitate

Cryoprecipitate is a concentrate prepared by freeze- thawing of plasma from a single donor. It is rich in factor VIII, fibrinogen and von Willebrand’s factor. Indications for cryoprecipitate transfusion include:
• haemophilia;
• von Willebrand’s disease
• fibrinogen deficiency, e.g. DIC


Factor VIII concentrate

This is used for treatment for haemophilia A.


Complications of blood transfusion: Immediate

Haemolytic transfusion reactions
This occurs with ABO incompatibility. Symptoms and signs include:
• pyrexia;
• dyspnoea;
• chest pain;
• severe loin pain;
• collapse;
• hypertension;
• haemoglobinuria;
• oliguria (often proceeding to acute renal failure); • jaundice; and
• DIC with spontaneous bruising and haemorrhage.


Complications of blood transfusion: Delayed

This occurs with low-titre antibody too weak to detect in a cross match and unable to cause lysis at the time of transfusion. The reaction usually occurs 5–10 days post transfusion. Symptoms and signs include:
• pyrexia;
• anaemia;
• jaundice; and
• haemoglobinuria.


Complications of blood transfusion: Reaction to white blood cells

Reaction to white blood cells usually results in a febrile reaction and is relatively common in patients who have had previous blood transfusions or pregnancy. Fever and flushing result soon after starting the transfusion. The reaction is due to recipient leucocyte antibodies. If a patient is known to have had a previous similar reaction, washed red cells should be given.


Complications of blood transfusion: Infection

Infection is unlikely with the present testing in the UK but may be a problem where testing is not carried out. Causes of infection include:
• HIV;
• hepatitis B;
• hepatitis C;
• CMV;
• malaria;
• syphilis; and
• prion disease, e.g. Creutzfeldt-Jakob disease


Complications of massive blood

Complications of massive blood transfusion include:
• fluid overload;
• cardiac arrhythmias due to cold blood;
• citrate toxicity with resulting hypocalcaemia;
• hypothermia;
• hyperkalaemia;
• metabolic acidosis because of acidity of stored
• haemorrhage due to coagulopathy unless FFP and
platelets are administered simultaneously;
• DIC; and
• ARDS/TRALI (transfusion-related acute lung


Autologous blood transfusion

Methods of reducing blood bank transfusion involve ‘recycling’ of patient’s own blood (autotransfusion). Some patients request this because they worry about getting infection from donated blood. Autotransfusion may be carried out in several ways.

1. Pre-donation. Blood is taken from the patient at weekly intervals prior to elective surgery. Up to 4 units may be taken over four weeks.

2. Normovolaemic haemodilution. Blood is collected immediately prior to surgery and replaced with colloid. Up to two litres can be removed safely from adults who are otherwise well. The blood
is fresh, contains viable platelets and clotting

3. Intra-operative blood salvage techniques. This
is useful when massive bleeding occurs in an uncontaminated operative field, e.g. ruptured aortic aneurysm or liver trauma. It is unsuitable where contamination occurs, e.g. in abdominal surgery where the bowel is breached. Blood spilled at operation is collected by suction, processed and re-infused (using a ‘cell saver’). The blood is anticoagulated and returned to the patient via a fine filter.


Lymphoid system:

Lymph nodes are discrete encapsulated structures, usually kidney-shaped, and range in diameter from a few millimetres to several centimetres. They are situ- ated along the course of lymphatic vessels and are numerous where these vessels converge, e.g. the root of the limbs, the neck, the pelvis and the mediastinum.

A lymph node has an outer capsule of connective tis- sue from which trabeculae pass into the deeper tissue (Fig. 10.4). Beneath the capsule is a space, the sub- capsular sinus into which the afferent lymphatics drain after penetrating the capsule. Lymph from the subcapsular sinus passes via the medullary cords to the hilum of the lymph node from which the efferent lymphatics drain. Both afferent and efferent vessels have valves which allow only forward flow. The node itself consists of an outer cortex and an inner medulla and contains lymphatic sinuses. There are three distinct microanatomical regions within a lymph node. These are:

1. the cortex: which contains either primary or secondary lymphoid follicles;

2. the paracortex: which is the T-cell-dependent region of the lymph node; and

3. the medulla: which contains the medullary cords and sinuses and also contains lymphocytes which are much less densely packed than in the cortex, together with macrophages, plasma cells and a small number of granulocytes.


Lymphoid system: Cortex

The cortex consists of primary lymphoid follicles which are unstimulated follicles, spherical in shape, containing densely packed lymphocytes. Secondary follicles are present after lymphocytes have been stimu- lated antigenically. These follicles have an outer ring of small B lymphocytes surrounding the germinal centre, which contains largely dividing lymphoblasts, macro- phages and dendritic cells. Antigen is trapped upon the surface of the dendritic cells and presented to ‘virgin’ B lymphocytes in the presence of T helper cells, and these B cells subsequently undergo a series of morpho- logical and functional changes. The function of germinal centres is to generate immunoglobulin-secreting plasma cells in response to antigenic challenge.


Lymphoid system: Paracortex

The paracortex is the T-cell-dependent region of the lymph node. When a T cell response occurs there is marked proliferation of cells in this area. The paracortex contains large number of T lymphocytes with a pre- dominance of helper/inducer cells. The cluster of differ- entiation (CD4) is expressed by helper/inducer T cells.


Lymphoid system: Medulla

Lymph enters the marginal sinus of the node and drains to the hilum through the sinuses which converge into the medullary region. The sinuses are lined by macro- phages which phagocytose foreign or abnormal par- ticles from the lymph passing through the node, i.e. the filtering function. Between the sinuses in the medulla lie the medullary cords which contain numerous plasma cells and are one of the main sites of antibody secretion within the lymph node.


Primary lymphoedema

This is a condition due to aplasia or hypoplasia of lymphatics. There are three types: congenital lym- phoedema or Milroy’s disease, which presents shortly after birth; lymphoedema praecox, which presents at puberty; and lymphoedema tarda, which presents around the age of 30.


Secondary lymphoedema

Lymphoedema may be secondary to result of damage to lymphatic channels by infection, surgery, radiotherapy, malignant infiltration, or trauma. Blockage of inguinal lymphatics by filarial parasites frequently causes gross oedema of the legs and, in the male, the scrotum. The resulting deformity is called elephantiasis.

Blockage of the lymphatic drainage from the small intestine usually occurs because of tumour involve- ment causing malabsorption of fats and fat-soluble substances. Blockage of lymphatic drainage at the level of the thoracic duct causes chylous effusions in the pleural and peritoneal cavities. At paracentesis or thoracocentesis, the fluid is opalescent because of the presence of numerous tiny fat globules (chyle).