Vascular neurology questions and answers - part 7

CLINICAL HEM ATOLO GY: ANSWER S 189 355. T he answer is C. T he intrinsic pathway of activation of the coagulation cascade includes factors VIII, IX, XI, and XII, along with prekallikrein, phospho-lipids, and high-molecular-weight kininogen. The common pathway includes phospholipids, factors V and X, prothrombin, and fibrinogen. Because the intrin-sic pathway requires contact activation, various methods of activation are used in performing this assay. Originally, the glass tube provided the contact activation, but now ellagic acid or kaolin produces better and more standard activation. The PTT is elevated in patients with lupus anticoagulant or those who are on heparin therapy, but it can also be elevated in patients with factor defi ciencies, particular-ly factors VIII and IX. Factor VII, along with tissue factor, belongs to the extrinsic pathway and does not influence the PTT. A low PTT is indeed an independent predictor of a hypercoagulable state. (Greer et al., Chapter 51) 356. T he answer is D. T he prothrombin time (PT) measures the activity of the extrinsic and common pathways of coagulation. The extrinsic pathway includes tissue factor and factor VII. The common pathway includes phospholipids, fac-tors V and X, prothrombin, and fibrinogen. Although the name of the test may in-correctly suggest that the test is most sensitive to prothrombin, the test is actually most sensitive to low levels of factors VII and X. The test is not affected by platelet levels. Unlike the PTT, the PT requires no activation. (Greer et al., Chapter 51) 357. T he answer is A. T he vitamin K–dependent factors, which are decreased by warfarin (Coumadin) and related agents, include prothrombin and factors VII, and X. Fibrinogen and factors VIII, XI, and XII are not vitamin K–dependent fac-tors. (Greer et al., Chapter 51) 358. T he answer is B. Fever is also present in 50% of thrombotic thrombocyto-penic purpura (TTP) patients. Many of the clinical manifestations of this disorder are caused by diffuse microangiopathic thrombotic occlusions, which can occur in the brain, kidney, and other organs. Idiopathic thrombocytopenic purpura (ITP) is frequently associated with lupus, but TTP is not. Th rombotic thrombo-cytopenic purpura has been associated with thienopyridine, generally ticlopidine, use. (Greer et al., Chapter 54) 359. T he answer is D. Although platelet inhibition and steroids are often used, their benefit is uncertain. Platelet transfusion is contraindicated, because it is as-sociated with worsening of renal function and neurologic complications. (Greer et al., Chapter 54) 190 CLINICAL HEM ATOLO GY: ANSWER S 360. T he answer is A. Essential thrombocytosis is not accompanied by poly-cythemia or the Philadelphia chromosome, both of which are features of polycy-themia vera. Aspirin is useful in reducing the symptoms of cerebral microthrom-bosis. Aspirin does increase the bleeding time more in patients with essential thrombocytosis than in normal patients, but it is considered the treatment of choice in some patients with essential thrombocytosis, particularly in those with erythromelalgia. (Greer et al., Chapter 57) 361. T he answer is C. Factor V Leiden is present in 3% to 7% of the general population, whereas the other hypercoagulable factors are present in 3% or less of the general population. Elevated anticardiolipin antibodies are also common, being present in 2% to 7% of the population, and mild homocystinemia is pres-ent in 5% to 10 % of the general population. When evaluating patients presenting with a first venous thromboembolism, factor V Leiden, hyperhomocysteinemia, LA, factor VIII elevation, and elevated anticardiolipin antibodies are each found in excess of 10% of these patients. Similar data are not available related to patients presenting with stroke or TIA. Von Willebrand’s disease is not a hypercoagulable state, but produces excess hemorrhage. (Greer et al., Chapter 61) 362. T he answer is C. Warfarin-induced skin necrosis occurs rarely in patients who are not on parenteral anticoagulation when started on large doses of war-farin. Protein C levels are reduced by warfarin before the vitamin K–dependent procoagulant factors, resulting in a worsening of the protein C–induced hyperco-agulable state. As warfarin reduces protein C levels, protein C defi ciency cannot be diagnosed in a patient on warfarin. Many patients with protein C defi ciency are asymptomatic and do not require specific treatment. The recommendation for warfarin therapy is 3 to 6 months following a first deep venous thrombosis (DVT). If recurrent DVT or life-threatening thrombosis occurs, lifetime warfarin should be considered. (Greer et al., Chapter 61) 363. T he answer is C. Ninety-two percent of individuals with activated protein C resistance (APC-R) have factor V Leiden mutation. Because APC-R testing is less expensive than is polymerase chain reaction (PCR) for factor V Leiden, it is the recommend screening test. Pregnancy, oral contraceptives, cancer, certain antiphospholipid antibodies, and other factors can also cause APC-R, so con-firmation by PCR for factor V Leiden mutation is necessary. Activated protein C resistance is sensitive but not specific. Patients with negative APC-R do not require PCR for factor V Leiden. Activated protein C resistance is not associ-ated with protein C deficiency or with antithrombin III deficiency. (Greer et al., Chapter 61) CLINICAL HEM ATOLO GY: ANSWER S 191 364. T he answer is D. Factor V Leiden mutation is associated with a two- to tenfold lifetime increase in the risk of venous thromboembolism. Although there is a notable absence of association with arterial thrombi, it is a risk factor for myocardial infarction in young women, particularly in smokers. This mutation is most common in individuals of European descent, and it is rare in those of Asian and African descent. The inheritance is autosomal dominant, similar to most other hypercoagulable states. Factor V Leiden is not an indication for lifetime anticoagulation after a thrombotic event, unless multiple events or one severe life-threatening event occurs. (Greer et al., Chapter 61) 365. T he answer is A. Factor VII has a half-life of only 4 to 6 hours. Loading doses will produce a more rapid fall in factor VII and an increased PT, but therapeutic anticoagulation is not reached until other factors with longer half-lives are also af-fected. Although the warfarin-induced tissue necrosis may be prevented by heparin, therapeutic anticoagulation is not reached earlier with loading doses. Even without warfarin load, the PT may increase after only 1 day of warfarin, but therapeutic an-ticoagulation requires a minimum of 4 to 5 days. Thus, heparin should be continued for 4 to 5 days after the initiation of warfarin therapy, even when the INR reaches standard therapeutic levels within a shorter time frame. (Greer et al., Chapter 54) 366. T he answer is A. T his patient has the classic clinical presentation for polycythemia vera. The hallmark of this disorder is an elevated hematocrit. Fre-quently, elevated leukocyte and platelet counts also will be present. Patients have facial rubor, leading to a complexion described as “ruddy.” Neurologic symptoms include headache, vertigo, visual disturbances, focal neurologic defi cits, and seizures. Retinal vascular engorgement and papilledema may occur because of sludging. A metabolic panel and an ANA will be of no help in making the ap-propriate diagnosis, although spurious elevation of potassium levels may occur with this disorder. Fibrinogen consumption can occur, with a corresponding de-crease of fibrinogen, but a fibrinogen level is not diagnostic for polycythemia vera. (Greer et al., Chapter 85) 367. T he answer is E. Phlebotomy has the advantage of immediately lower-ing the red cell mass. Some patients can be treated with repeated phlebotomy alone. When phlebotomy does not adequately control the disorder, hydroxyurea is the most widely used treatment of polycythemia vera. Interferon-α is another effective agent. Steroids are of no value. Platelet inhibition has been studied, in combination with phlebotomy, to reduce the incidence of thrombotic complica-tions of polycythemia vera, with confl icting results, but there has been no study of platelet inhibition alone. (Greer et al., Chapter 85) 192 CLINICAL HEM ATOLO GY: ANSWER S 368. T he answer is C. Heparin-induced thrombocytopenia (HIT), an immune-mediated drug reaction, is caused by antibodies against complexes of platelet fac-tor 4 (PF4) and heparin. It presents with a low platelet count (<150,000 per cubic millimeter or a relative decrease of >50% of baseline) in patients on parenteral heparin. Heparin-induced thrombocytopenia is about ten times more common with unfractionated heparin than with low-molecular-weight heparin. Arterial or venous thrombotic complications develop in 20% to 50% of patients with HIT. The mortality of HIT related thrombosis is high, and heparin therapy should be discontinued when HIT is diagnosed. When HIT is diagnosed by serologic or functional assays, the patient can be parenterally anticoagulated with direct thrombin inhibitors or heparinoids. (Arepally & Ortel, N Engl J Med 2006; Pohl et al., Neurology 2005) 369. T he answer is D. T he coagulation system is triggered by the formation of the tissue factor–factor VIIa complex at the site of vascular injury. Drugs that block this complex are potent anticoagulants, but are still under development. Propagation of the thrombus occurs when factor IXa binds to its cofactor VIIIa, to form a complex that activates factor X. Factor Xa binds to its cofactor Va to form prothrombinase, which converts prothrombin to thrombin. Thrombin generation is blocked by drugs targeting these propagating coagulation factors. Th rombin ac-tivates platelet-bound factor XI, promoting factor Xa generation. In the fi nal step of coagulation, thrombin converts fibrinogen to fi brin. Low-molecular-weight heparin and unfractionated heparin are indirect thrombin inhibitors that cata-lyze natural thrombin inhibitors but do not act against fi brin-bound thrombin. The parenteral direct thrombin inhibitors, hirudin, argatroban, and bivalirudin, inactivate fibrin-bound thrombin directly with a more predictable anticoagulation action than do the indirect inhibitors. The only approved thrombin inhibitors are parenteral (as of 2007), although oral agents are being investigated in clinical tri-als. Dabigatran is an oral direct thrombin inhibitor being studied for the preven-tion of stroke in patients with atrial fibrillation. Fibrin interacts with the platelet at the glycoprotein IIb/IIIa receptor to form a cross-linking platelet–fi brin network. (Weitz & Bates, J Thromb Haemost 2005) 370. T he answer is D. Patients who develop HIT and continue to need antico-agulation should be treated with the intravenous direct thrombin inhibitor arg-atroban (Novastatin). The oral direct thrombin inhibitor dabigatran is still being tested for safety and efficacy and is not yet approved for clinical use. Unfraction-ated heparin, low-molecular weight-heparin, and glycoprotein IIb/IIIa inhibitors should not be used in patients with HIT. (DiNiso, N Engl J Med 2005) CLINICAL HEM ATOLO GY: ANSWER S 193 371. T he answer is A. Aspirin resistance is the inability of aspirin to reduce the platelet activation and aggregation initiated by the production of thrombox- ane A2. The correlation of the laboratory measure of resistance to the clinical outcome of reduction of vascular events is under investigation, as are the thera- peutic options when an aspirin treatment failure occurs. Multiple etiologies for aspirin treatment failure range from medication noncompliance to many causes of platelet alteration. No standard, reproducible laboratory measure of the anti-platelet effects of aspirin exists, although methods exist to measure thrombox-ane production and thromboxane-dependent platelet function. Resistance to the antiplatelet effects of clopidogrel is also being investigated, but as with aspirin, the clinical relevance is as yet uncertain. (Hankey & Eikelboom, Lancet 2006; Helgason et al. Stroke 1994) 372. T he answer is A. Von Willebrand’s disease, the most common inherited bleeding disorder, is caused by a quantitative (type 1 and 3) or qualitative (type 2) defect of vWF. Patients are treated with desmopressin or plasma concen-trates containing factor VIII and vWF. Bernard-Soulier’s syndrome, along with May-Hegglin’s anomaly and gray platelet syndrome, is an inherited giant-plate-let disorder characterized by abnormally large platelets, thrombocytopenia, and bleeding tendency. Hemophilia A (a deficiency of factor VIII) is more common than hemophilia B (a deficiency of factor IX), which is also known as Christmas’ disease, named after the first patient diagnosed with this deficiency during the 1950s. (Franchini, Hematology 2005; Hayward et al., Haemophilia 2006; Peyvandi et al., Haemophilia 2006) 373. T he answer is C. Although different studies show some variability in results, these gene mutations do not appear to be strong risk factors for ischemic arterial stroke, either in young people or in patients with atrial fibrillation. Although some association exists with ischemic stroke in patients with PFO, this may relate to their propensity for venous thrombosis. Although these mutations have differing risk of venous thrombosis, more with factor V Leiden and prothrombin than with methy-lenetetrahydrofolate reductase, in combination, the risk is additive. (Almawi et al., J Thromb Thrombolysis 2005; Berge et al., Stroke 2007; Lopaciuk et al., Clin Appl Thromb Hemost 2001; Wu et al., Thromb Haemost 2005) ... - tailieumienphi.vn