Haematological Disorders and Blood Transfusion
THE PHYSIOLOGY OF BLOOD
Blood Coagulation
The physiology of haemostasis involves a complex interaction between the endothelium, clotting factors and platelets. Normally, the subendothelial matrix and tissue factor are separated from platelets and clotting factors by an intact endothelium. However, when a blood vessel is damaged, vasospasm occurs, which reduces initial bleeding and slows blood flow, increasing contact time between the blood and the area of injury. Initial haemostasis occurs through the action of platelets. Circulating platelets bind directly to exposed collagen with specific glycoprotein Ia/IIa receptors. Von Willebrand factor released from both endothelium and activated platelets strengthens this adhesion. Platelet activation results in a shape change, increasing platelet surface area, allowing the development of extensions which can connect to other platelets (pseudopods). Activated platelets secrete a variety of substances from storage granules, including calcium ions, ADP, platelet activating factor, von Willebrand factor, serotonin, factor V and protein S. Activated platelets also undergo a change in a surface receptor, glycoprotein GIIb/IIIa, which allows them to cross-link with fibrinogen. In parallel with all these changes, the coagulation pathway is activated and further platelets adhere and aggregate (Fig. 13.1).
FIGURE 13.1 Clotting processes. From Curry ANG, Pierce JMT. Continuing Education in Anaesthesia, Critical Care & Pain 2007; 2(2): 45–50.
The classical description of coagulation pathways includes an intrinsic pathway and an extrinsic pathway in which clotting factors are designated with Roman numerals (Fig. 13.1). Each pathway consists of a cascade in which a clotting factor is activated and in turn catalyses the activation of another pathway. The intrinsic pathway involves the sequential activation of factors XII, XI and IX. The extrinsic pathway involves the activation of factor VII by tissue factor, and is sometimes called the tissue factor pathway. Of the two pathways, the extrinsic pathway is considered to be the more important because abnormal expression of the intrinsic pathway does not necessarily result in abnormal clotting. The intrinsic pathway may have an additional role in the inflammatory response.
The following steps can be conceptualized (Fig. 13.1):
Common laboratory tests used to investigate coagulation include:
The activated prothrombin time (PT), which tests for factors involved in the extrinsic coagulation pathway (prothrombin, factors V, VII, X), normal range 12–14 s, but often expressed as a ratio (the international normalized ratio, INR)
The activated partial thromboplastin time (APTT, also known as the kaolin cephalin clotting time, KCCT), which tests for factors present within the intrinsic pathway (including factors I, II, V, VIII, IX and X), normal range 26–33.5 s, often also expressed as a ratio (APTTR)
Thromoboplastin time (TT), which tests for the presence of fibrinogen and the function of platelets, normal range 14–16 s
HAEMATOLOGICAL DISORDERS AND THEIR IMPACT ON ANAESTHESIA
Anaemia occurs as a result of decreased red cell production or increased loss due to bleeding or destruction. A number of congenital or acquired conditions can result in anaemia (Table 13.1). Anaemia is defined as a haemoglobin less than 13 g dL− 1 (men) or 12 g dL− 1 (women), but the level of anaemia at which physiological dysfunction occurs in everyday life, or under the stress of surgery, is unclear.
TABLE 13.1
*Causes of MAHA include vasculitis, disseminated intravascular coagulation (DIC), HELLP syndrome (Haemolysis, Elevated Liver enzymes, Low Platelets) and thrombotic thrombocytopaenic purpura/haemolytic uraemic syndrome (TTP/HUS) (see Table 13.2).
microcytic, hypochromic anaemia (anaemia with a low mean cell volume, MCV < 78 fL, and low mean cell haemoglobin, MCH < 27 pg); common causes include iron deficiency anaemia, chronic blood loss, anaemia of chronic disease, thalassaemia or sideroblastic anaemia.
macrocytic anaemia (MCV < 100 fL); common causes include vitamin B12 or folate deficiency/malabsorption, alcoholism, liver disease, myelodysplasia or hypothyroidism. If the reticulocyte count is high (> 2.5%), acute blood loss or haemolytic anaemia may be considered.
normocytic normochromic anaemia (normal MCV and MCH); common causes include anaemia of chronic disease, aplastic anaemia, haematological malignancy, or bone marrow invasion or fibrosis. If the reticulocyte count is high, this may also represent acute blood loss or haemolysis.