Which ONE of the following is TRUE regarding complications associated with the use of heparin?
Answer: C: The onset of HIT is usually 5–10 days after initiation of heparin treatment but may occur sooner in patients who have been previously exposed to heparin. Heparin-induced thrombocytopaenia is caused by the formation of autoantibodies directed against both heparin and platelet factor IV. This causes activation of platelets leading to both thrombocytopaenia and a tendency for thrombosis. Thromboembolic complications can be venous, arterial,or both, and can be life or limb threatening. The platelet count usually returns to normal 4–6 days after heparin has been stopped and the risk of thrombosis is highest during this recovery phase. HIT more commonly occurs with UFH but can also occur with LMWH, albeit approximately 10 times less frequent. Therefore, anticoagulation with a nonheparin anticoagulant, such as fondaparinux, and not LMWH is recommended when HIT is suspected, even in the absence of thrombosis.
Bleeding is one of the major complications associated with the use of heparin. Protamine can reverse the anticoagulant effect of UFH and is given as 1 mg per 100 U of total amount of heparin given intravenously within the past 3 hours; although UFH half-life is dose-dependant, its anticoagulation effect can last up to 3 hours. In general, LMWH preparations cause less bleeding than UFH. Protamine will not reverse the anticoagulant effect of LMWH completely as it does not neutralise the inhibitory effect of LMWH on factor Xa. However, it still has a partial effect as it neutralises the inhibitory effect on thrombin. Enoxaparin is a LMWH commonly used in the ED. Protamine is given as 1mg intravenously for every 1mg of enoxaparin given in the previous 8 hours. If 8–12 hours since last dose of enoxaparin dose, give protamine 0.5 mg intravenously for every 1 mg of enoxaparin given.
Reference:
Regarding thrombolytic therapy for acute ischaemic stroke, which ONE of the following is TRUE?
Answer: B: rtPA, a second-generation fibrinolytic, is the only approved treatment for acute ischaemic stroke. The total dose of rtPA is 0.9 mg/kg, with a maximum dose of 90 mg; 10% of the dose is administered as a bolus, with the remaining amount infused over 60 minutes. No anticoagulants or antiplatelet agents should be given in the initial 24 hours following treatment; this recommendation is mainly based on the initial NINDS protocol.
Tenecteplase, a third-generation fibrinolytic, is a modified version of rtPA that is more fibrin-specific, with potentially fewer bleeding complications, and has a longer half-life, which allows for a single-weight bolus dosing over 5–10 seconds. It has been approved for use in myocardial infarction, in which it is associated with fewer systemic bleeding complications than alteplase. However, there are currently no randomised controlled trials of tenecteplase in acute ischaemic stroke and rtPA remains the only approved treatment. A previous pilot dose-escalation study with intravenous tenecteplase showed promise as a potentially safer alternative. A subsequent phase IIB/III trial of tenecteplase in acute ischaemic stroke was unfortunately prematurely terminated due to slow enrolment and no convincing conclusions could be made.
References:
Regarding laboratory tests in the evaluation of anaemia, which ONE of the following is FALSE?
Answer: A: The mean corpuscular volume (MCV) is the most useful guide to the possible aetiology of anaemia and is used to classify the anaemic process as microcytic, normocytic and macrocytic. The RDW measures the size variability of the RBC population and is useful in distinguishing the deficiency anaemias (iron, vitamin B12, or folate) from other causes. It may be increased in early deficiency anaemia (iron, vitamin B12 or folate) even before the MCV becomes abnormal. RDW is also useful in differentiating iron deficiency (high RDW) from thalassaemia (normal RDW). Thalassaemia is a hereditary disorder caused by defective synthesis of globin chains, resulting in an inability to produce normal adult haemoglobin. The hallmark of thalassaemia is microcytic, hypochromic haemolytic anaemia.
The direct Coombs’ test is used to detect antibodies on the RBCs. It is positive in autoimmune haemolytic anaemia, transfusion reactions and some drug-induced haemolytic anaemia. The indirect Coombs’ test is used to detect antibodies in the serum and is routinely used in compatibility testing before transfusion.
Which ONE of the following statements is TRUE regarding sickle cell disease (SCD)?
Answer: D Severe acute pain due to a vaso-occlusive crisis is the most common manifestation of SCD requiring hospital admission. Acute pain frequently occurs spontaneously, but may be precipitated by hypoxia, dehydration, infections, cold weather or stress. Initial management should be aimed at providing rapid pain control and hydration. Opioids are usually required for severe pain but NSAIDs may have an additive role in combination with opioids for severe pain. There is currently no evidence to guide clinicians regarding the optimal choice of intravenous fluid. Dextrose (5%) can induce hyponatraemia, which may be of marginal benefit during painful crises, although significant hyponatraemia should be avoided. Once pain is controlled, the underlying cause should be assessed and further investigations should be undertaken for atypical pain. Although supplemental oxygen is commonly used routinely for painful crises, it has not been proven to be of routine benefit. Current recommendations support the use of oxygen if oxygen saturation is <95%. SCD patients are more susceptible to serious infection, especially with encapsulated organisms, and broad-spectrum antibiotics should be started if the patient is febrile (temperature >38°C), generally unwell, has chest symptoms or signs, or infection is suspected for some other reason. Low-grade fever is common during an acute crisis. White cell counts are routinely elevated in SCD and leucocytosis does not always equate with infection. A WCC >20,000 with an increased number of bands is not typical for sickle cell crises alone and a potential infection should be considered.
A serious complication is aplastic crisis. This is usually caused by infection with parvovirus B-19. This virus infects RBC progenitors in bone marrow, resulting in impaired cell division for a few days. A subsequent very rapid drop in haemoglobin occurs with few or no reticulocytes present. The leukocyte and platelet counts are usually normal. The condition is self-limited, with bone marrow recovery occurring in 7–10 days, followed by brisk reticulocytosis. Transfusion may be required in the interim.
Acute splenic sequestration is a medical emergency characterised by the onset of life-threatening anaemia with rapid enlargement of the spleen and high reticulocyte count. Treatment of the acute episode requires early recognition, volume resuscitation and aggressive transfusion support. Blood for transfusion should be leucodepleted and matched for Rh (C, D and E) and Kell antigens.
Regarding idiopathic thrombocytopaenic purpura (ITP), which ONE of the following is TRUE?
Answer: A: ITP is an acquired autoimmune disease, often precipitated by intercurrent viral infections that result in the rapid destruction of platelets. Patients usually present with petechiae and/or purpura that is flat, with the rest of the physical examination normal. Palpable petechiae/purpura suggests vasculitis, subacute bacterial endocarditis (SBE), systemic lupus erythematosos (SLE) or rheumatoid arthritis. Occasionally, a spleen tip may be palpable, but prominent hepatosplenomegaly or lymphadenopathy should raise the suspicion of an alternative diagnosis. The laboratory hallmark of ITP is an isolated thrombocytopaenia with normal white and red blood cell counts. Review of the peripheral blood smear is important to ensure the presence of normal white blood cell morphology and differential and normal red blood cell morphology. The peripheral smear typically shows a reduced number of platelets that are large and well-granulated, suggesting a platelet destructive state. The presence of any other abnormality on peripheral smear would suggest an alternate diagnosis.
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