Coagulation Cascade Testing And Factor

Explain the practice and techniques to detect the presence of

There are various tests of the coagulation cascade that can be used to detect the factor specific coagulation inhibitors. These are in vitro laboratory tests that measure different points between the times taken when the coagulation cascade is activated to the time the fibrin is generated. The tests include; the prothrombin time (PT) and the activated partial thromboplastin time (aPTT). The results are then evaluated based on the elevations in the respective assays. Depending on the results, mixing studies are then performed to determine the presence of specific coagulation inhibitors.

The presence of factor specific inhibitors is usually indicated by prolonged activated partial thromboplastin time (aPTT) or the prothrombin time (PT) results, depending on the exact factor that has been targeted by the coagulation inhibitor. The clinical signs usually entail abnormal clotting and other complications in bleeding.

Given the fact that at times the test results may be abnormal as a result of factor deficiency or the presence of an inhibitor, a mixing study is then carried out to differentiate. If from the results of the mixing study, the previous abnormality is fully corrected, then it is a factor depletion problem, while if the result remains the same or there is only partial correction, then there is presence of an inhibitor to any of the intrinsic factors.

Explain the principles and practice of techniques to assess specific coagulation factor deficiencies (e.g. one stage clotting assays) 200 words

The in vitro tests of prothrombin time (PT) and activated partial thromboplastin time are the most commonly applied techniques for the assessment of specific coagulation factor deficiencies. Overall, the hemostasis process happens in three phases; the primary hemostasis through the vascular platelet, the formation of clot through coagulation cascade activation and finally control mechanisms that stop the propagation of the clot and restricts the coagulation to the endothelial rupture.

The principle behind the aPTT and PT tests is to measure the time taken for fibrin generation. Abnormalities in one of the two tests or both, therefore indicates coagulation deficiencies. The aPTT test results are usually abnormal when there are reduced quantities of coagulation factors XII, IX, VII and V. The aPTT is usually prolonged in patients who are deficient of factor VII, associated with classic hemophilia A and factor IX which is associated with hemophilia B. Prolonged PT results on the hand indicates the deficiency of factor VII. This test is particularly more sensitive than the aPTT and the results can be prolonged when there is just a small drop in the levels of factor VII.

Explain the normal reference values and the significance of any abnormal results. 200 words

The laboratory tests of coagulation include; platelet counts, the bleeding time, prothrombin time, activated partial thromboplastin time, thrombin time and the fibrinogen levels. The platelet count helps in the assessment of any coagulation abnormalities by reflecting the quantity of the blood platelets. The normal platelet count is usually in the range of 150,000-440,000/mm3. Abnormalities, in which counts are less than 150,000/mm3 are normally associated with the thrombocytopenia condition. The bleeding test on the other hand is used to assess the normal functioning of the platelets and to determine surgical bleeding. The normal time range is given by 2-9 min, the duration of bleeding after a cut has been made. However, since this can be affected by numerous factors and not necessarily deficiency or presence of inhibitors, its use has been declining. The PT is meant to show the integrity of extrinsic coagulation pathways. Results can be interpreted by using control values, international normalized ratios, PT ratios or the PT index. The most common measurement however is the

nternational normalized ratios (INR). The normal PT range in this case is indicated as between 0.9-1.2 s, prolonged results or abnormalities may indicate liver disease, vitamin K deficiencies, or factor VII deficiencies. The normal range for the aPTT is usually between 25-35 s, in which any abnormalities may be an indication of most of the factor deficiencies except for the factor VII.

What are the relevant internal quality control and quality assurance procedures associated with bleeding disorders? 150 words.

The internal quality control and quality assurance procedures in coagulation laboratories are essential for ensuring the test results are accurate. There are various types of quality controls (QCs). These include; the incorporation of pooled patient plasma in the quality control program, running of quality checks at the beginning of every shift, followed by ensuring of maintenance of the reagent changes during the shift during every repeat sample. The frequency of the internal quality check running is however determined by various factors including manufacturer recommendations, the stability of the tests and the clinical impact of abnormal results. Also, the whole processes are usually monitored by using some preset limits on performance and standard deviations. Failure actions include repeating the whole quality check and assurance procedure in which the test results come different then a repeat analysis of all the samples has to be partaken from the last acceptable quality check.

Hemophilia is the most commonly known coagulation factor deficiency. In particular, individuals with deficiencies in the clotting factor VII usually have the hemophilia A while those with deficiencies in factor IX have the hemophilia type B. On the other hand, those who are affected by the von Willebrand disease may be deficient in the von Willebrand factor (vWF), coagulation factor VIII or at times having the von Willebrand factor that is not correctly functioning.

The coagulation abnormalities for people with type A hemophilia include bleeding episodes that happen after injuries or at times spontaneous bleeding episodes that occur without any obvious cause, often into the joints or muscles. Also known as the Christmas disease, hemophilia B abnormalities are kind of similar to those of hemophilia A ranging from injury caused bleeding to spontaneous bleeding in the joints or muscles for the more severe cases.

Write a reflection of this essay.

The essay on blood disorders has presented me with an opportunity to further gain knowledge on the various coagulation factor deficiencies and inhibitors. While researching on the essay, I have been able to reflect on previously learnt methods in class while at the same using other existing scholarly journals to look for information on the subjects. As such I have been able to better understand various issues in relation to coagulation and bleeding disorders.

For now, I clearly understand the practice and techniques that can be used to detect and differentiate the presence of coagulation factor deficiencies or inhibitors. The clinical significance if the tests, the principles behind and the consequent meaning of the results whether normal or abnormal are very important for the diagnosis of any bleeding disorders. For instance, the complete blood count, prothrombin time and activated partial thromboplastin time assays are very important for the diagnosis of bleeding disorders.

What is meant by the term lupus anticoagulant

The abnormality in the prolonged results of the PT and aPTT tests that still remains uncorrected in the mixing study, may be an indication of the condition that is referred to as the lupus anticoagulant. They are antibodies that are produced by the body’s immune system which in turn act against some cells in the body.

The antiphospholipid antibodies can be inhibitors against the respective factors in the coagulation cascade. They usually result in a prolonged time taken for coagulation, from the time the fibrin is activated. A good example is the factor VIII inhibitor antibody that comes when patients with the hemophilia A condition are treated with the factor concentrate of factor VIII. The antiphospholipid antibody against the factor degrades the fibrin hence resulting in longer time. Prolonged aPTT and PT results can also reflect the lupus anticoagulant. The lupus anticoagulant forms part of the primary antiphospholipid antibodies. These antibodies are associated with an increased risk in thrombosis. It combines with the phospholipid layer thereby also acting as an inhibitor by prolonging the coagulation cascade, just like the other antiphospholipid antibodies.

The coagulation screening tests that may be affected by the lupus anticoagulant include the activated partial thromboplastin time (aPTT) and the prothrombin time (PT). Abnormal results from these tests, usually more prolonged time than the normal range, can be seen with the lupus anticoagulant. The test results are prolonged because the antibody pools with the phospholipids that are on the surface of the respective test reagents that are used in the activated partial thromboplastin time (aPTT) and sometimes the prothrombin time (PT) tests. The lupus anticoagulant is usually associated with thrombosis clinical signs rather than the bleeding symptoms. These tests usually measure the time that is taken for the generation of fibrin. The lupus anticoagulant combines with the activating agent which in turn results in a prolonged time. This is because the anticoagulant limits the activation of the factor XII which is necessary for the normal functioning of the coagulation cascade.

The techniques used for the detection of lupus anticoagulants usually seem odd and confusing since there exist no single test for its detection and thus it cannot be directly measured. The initial tests usually entail the use of reagents containing phospholipids in the prothrombin or activated thromboplastin tests. Both of the tests measure the exact time it takes for the sample of the plasma to clot in which prolonged results may reflect lupus anticoagulant. Depending on the results, follow ups may be performed to either confirm or exclude the existence of lupus anticoagulants. Even though the lupus anticoagulants were named such because they were first observed in patients with the lupus condition,` the testing for lupus anticoagulants is limited in that it can’t be used to diagnose the autoimmune disorder. Moreover, the lupus anticoagulants may also be absent from individuals with lupus.

The results of the lupus anticoagulant tests may reflect presence or absence of the antibodies. The tests usually begin with the PT and aPTT in which normal values lies between the ranges 0.9-1.2 s and respectively. Any prolonged results or abnormalities form the basis for initial LA testing. Sometimes the result may be normal because the test wasn’t sensitive enough to detect lupus anticoagulants which in turn calls for the LA-sensitive PT or aPTT tests (PTT-LA). Since prolonged results may indicate either presence of LA or factor deficiencies, other tests are then done which include coagulation factor assays, blood count, and thrombin time. The factor assays are used to rule out factor deficiencies while the low platelet counts can reflect the lupus anticoagulants.

Alongside the appropriate clinical features and procedures, the diagnosis of the lupus anticoagulant (LA) and other antiphospholipid antibodies requires positive results from the clot based assays that is ensured only through the maintenance of high quality internal quality control and internal quality assurance procedures. Some of these procedures as discussed herein are very crucial for the correct diagnosis and thence appropriate management of the lupus anticoagulants.

To this end, it is recommended that the diagnosis of LA be carried out through two main processes, that is, the diluted Russell viper venom time (dRVVT) and the LA sensitive partial thromboplastin time (PTT-LA). This is to make sure that the risk of obtaining any false positive results is contained. Some other factors to be considered as a diagnostic utility entail the timing of the tests, the standardization procedures, the interpretation of the results and finally the preanalytical variables.

In general, the research and essay on the lupus anticoagulant and other antiphospholipid antibodies has presented me with an opportunity to learn and gain solid information on autoimmune disorders and their effect in the coagulation cascade. I have learnt a great deal about how the lupus anticoagulant and other antiphospholipid antibodies. Sometimes the coagulation screening test results such as the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) may be abnormal, that is, they can be prolonged without an evidence of any bleeding. This is particularly observed for patients who suffer from the systemic lupus erythematosus. These abnormal results may reflect the lupus anticoagulant. The test results are prolonged because the antibody combines with the phospholipids that are on the surface of the respective test reagents that are used in the activated partial thromboplastin time (aPTT) and sometimes the prothrombin time (PT) tests. The information on the principles behind the clinical diagnosis of the lupus anticoagulant and other antiphospholipid antibodies is very useful, especially when designing procedures that shall ensure the correct results are obtained to offer the appropriate medical intervention.

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