Haematology Flashcards
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
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
procedure
• consumptive coagulopathy, e.g. DIC; and
• platelet counts of 50,000 109/L are adequate for
haemostasis.
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 Immediate 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.
