A 72-year-old male is admitted to the intensive care unit after undergoing aortic valve replacement for severe aortic stenosis. He was successfully weaned from bypass, required no blood products, and received appropriate protamine reversal. In the intensive care unit, he has been having persistent drainage from the thoracotomy tubes. A complete blood count (CBC) shows a hematocrit of 40% and platelet count of 150,000/mm3 . Coagulation studies including a thromboelastogram (TEG) are sent.
Based on the results of the TEG, which of the following would be the best treatment option?
Correct Answer: A
Thomboelastogram, or TEG, is a whole blood, point-of-care test that analyses viscoelastic proprieties of evolving clot in the patient’s whole blood and can provide information about fibrin formation, platelet activation, and clot retraction, therefore assisting in identifying the cause of coagulopathy. Unlike the more traditional laboratory tests such as PT and PTT, which give a general state of the extrinsic and intrinsic pathways, TEG provides distinct values as well as a graphical representation of various stages in clot formation (Figure below).
R-time is the duration of time from the application of the blood sample until the clot reaches a graphical amplitude of 2 mm, in other words, the time elapsed between clot formation and a predetermined and consistent size. The initiation of clot formation is dependent on circulating, function clotting factors from both the intrinsic and extrinsic pathways. A normal Rtime is 5 to 10 minutes, whereas a value less than 5 minutes implies hypercoagulability, and conversely, a value greater than 10 minutes indicates either a quantitative or qualitative deficiency in clotting factors. Treatment for prolonged R-time typically is Fresh Frozen Plasma, or factor concentrate in the setting of known factor deficiency (ie Hemophilia).
K-time represents the time elapsed between the conclusion of R-time and a graphical amplitude of 20 mm. Because the K-time is the duration between an initial amplitude (2 mm) and final amplitude (20 mm), this provides a quantitate assessment of the speed of clot formation. Thrombin catalyzes the conversion of fibrinogen to fibrin, which adheres the platelet plug, strengthening it, and finalizing the clot formation. A prolonged Ktime indicates inadequate circulating fibrin and is treated with either fibrinogen concentrate, or cryoprecipitate.
Alpha angle is a measurement of the speed of clot strengthening via fibrin cross-linking. It is formed by a tangential line originating from the start of K-time and intersecting the upward slope of the graph. A decreased alpha angle is similar to a prolongation of K-time and is treated in a similar manner.
MA is the greatest width between the two arms of the curve and represents overall clot strength. As the available platelets continue to form clot, which is subsequently stabilized by fibrin cross-links, the strength of the clot increases and the arms of the curve move farther apart. Eventually, the clot begins to degrade and the arms start sloping downwards. This transition point marks the MA. MA is a surrogate for platelet function, where a decreased MA suggests either inadequate supply (ie postcardiac bypass thrombocytopenia) or suboptimal function (ie liver disease). A decreased MA is treated with platelets.
This patient has a decreased MA suggesting poor clot strength likely from platelet deficiency. So, the best treatment option based on the TEG would be to administer platelets.
Sample TEG demonstrating normal coagulation morphology with normal values:
A 63-year-old female with known lower-extremity deep vein thrombosis (DVT) is admitted to the intensive care unit after presenting with shortness of breath and chest pain. Imaging is negative for a pulmonary embolism, and blood tests including a CBC and serum electrolytes are normal. She is started on supplemental oxygen and a heparin infusion titrated to aPTT of 60 to 90 seconds. On admission day 7, her platelet count is found to have decreased from 150,000/mm3 to 62,000mm/ 3 over a 24-hour period. To assist in making the diagnosis, you calculate the patient’s 4-T score.
Which of the following is NOT a part of the 4-T score?
Correct Answer: D
Under normal conditions, Heparin binds to Antithrombin III (AT-3), which inactivates thrombin and Factor Xa causing a relative state of hypocoagulability. Intermittent bolus dosing is beneficial for patients at risk for thromboembolic events such as patients undergoing prolonged surgery. For patients with known DVT/PE, or other vascular thrombi, a continuous infusion may be utilized to prevent additional clot formation as well as enhance existing clot degradation. However, exposure to heparin may cause an autoimmune reaction where IgG-mediated antibodies bind to Heparin-PF4 complexes resulting in platelet activation and the formation of microthrombi and eventual thrombosis. The microthrombi consume existing platelets and results in thrombocytopenia. This entity is referred to as Heparin-induced thrombocytopenia/thrombosis (HIT).
One of the ways to predict the likelihood of HIT is to calculate the 4-T score. The 4-T score consists of four criteria graded on a 0 to 2 scale as shown in the table below. Scores of 0 to 3, 4 to 5, and 6 to 8 correspond to low, moderate, and high risk for HIT respectively. The negative predictive value of a low 4-Ts score has been found to be as high as 99%; meanwhile the positive predictive value of a high score is only 64%. For patients with thrombocytopenia and a moderate or high 4-Ts score, further testing is necessary to establish the diagnosis of HIT.
Estimating the likelihood of HIT: the “4-Ts” score:
Adapted from Ahmed I, Majeed A, Powell R. Heparin induced thrombocytopenia: diagnosis and management update. Postgrad Med J. 2007;83(983):575-582.
All patients with a presumptive diagnosis of HIT should have laboratory testing for HIT antibodies. This testing is challenging because HIT immunoassays (eg, enzyme-linked immunosorbent assay for antiplatelet factor 4 [PF4] antibodies) are readily available but not very sensitive or specific. Functional assays such as a SRA and Heparin-induced Platelet aggregation (HIPA), which measure the ability of patient serum to activate test platelets in the presence of heparin, are definitive but may take several days to return. The SRA is more sensitive than HIPA (95% vs 35%-85%), but is a more technically challenging test to perform.
Given the morbidity associated with HIT, prompt treatment is required to prevent further thrombus formation and worsening thrombocytopenia. Regardless of the likelihood of diagnosis, the first step in treatment is to immediately discontinue any heparin infusion, or heparin-coated products. Because HIT causes a functional hypercoagulable state, platelet transfusions should be withheld unless clinically indicated for significant bleeding or operative risk. Although awaiting the normalization of the platelet count, patients should be initiated on nonheparin anticoagulants, such as direct thrombin inhibitors (eg Argatroban, bivalirudin), fondaparinux, or factor Xa inhibitors (apixaban, rivaroxaban, etc.). Patients should be watched closely for bleeding as well as complications of thrombosis.
After calculating a 4-T score of 6, you proceed to obtain confirmatory testing to support your diagnosis. A Heparin PF-4 antibody test is positive, and heparin-induced serotonin release assay (SRA) is under process. Given the presumptive diagnosis, which of the following treatment strategies would be most appropriate?
Correct Answer: B
A 32-year-old male presents to the hospital complaining of progressive fatigue, productive cough, and intermittent epistaxis. His initial evaluation is significant for left lower lobe consolidation on chest X-ray and a temperature of 38.7°C. During attempts to obtain peripheral venous access, he bruises easily and missed attempts bleed for over 2 minutes. A CBC and coagulation studies are obtained and are as follows:
He is subsequently admitted to the ICU where broad spectrum antibiotics are initiated, and a bone marrow aspirate (BMA) is obtained, which shows finding consistent with acute myeloid leukemia.
Which of the following is the best initial treatment option for this patient?
This patient most likely has Acute promyelocytic leukemia (APL), a variant of Acute Myelogeneous Leukemia (AML) given his presentation with bleeding diathesis and the elevated PT and aPTT with BMA findings of AML. APL can cause acute Disseminated Intravascular Coagulopathy (DIC), which may be life-threatening. DIC is a consumptive coagulopathy; activation of the clotting cascade results in the development of thrombi, which in turn activate the fibrinolytic pathway resulting in accumulation of fibrin degredation products (FDP). FDP inhibits further fibrin clot formation and bleeding ensues.
It is critical to start treatment with ATRA without delay as soon as the diagnosis is suspected, and before definitive confirmation of the diagnosis has been made. If the diagnosis is not confirmed, ATRA can be discontinued and treatment changed to that used for other types of AML. Transfusion of blood products, specifically platelets may be ineffective owing to the high rate of platelet consumption caused by DIC. Administration of red blood cells may be indicated for patients experiencing large volume blood loss, although this is rarely seen in the absence of trauma. Fresh Frozen Plasma may be given to replenish clotting factors and Vitamin K can cause an increase in Vitamin-K–dependent clotting factors that can further assist in reversing the coagulopathy. However, the initial therapy that can be lifesaving in these patients is administration of ATRA.
A 29-year-old male is admitted to the intensive care unit after undergoing an uncomplicated laparoscopic splenectomy for idiopathic thrombocytopenic purpura. On post-op day 2, he is recovering well, is afebrile, is hemodynamically stable, and has no complaints. Routine laboratory test results are sent, which are significant for a platelet count of 654,000/µL.
What is the most likely cause of thrombocytosis in this patient?
Thrombocytosis is defined as platelet levels more than 450,000/µL and can be seen in sepsis, hematologic malignancy, or postsplenectomy. This patient most likely has a postsplenectomy-reactive thrombocytosis. As the spleen is a major site for platelet regulation and removal, thrombocytosis is seen in the acute postsplenectomy period and normalizes over time, typically reaching normal levels within 1 month.
Complications arising from the thrombocytosis have been reported and are most commonly thrombotic events in the mesenteric and hepatic vasculature, although rare cerebral and cardiac occlusions have been reported. Treatment of thrombocytosis is dependent on the presentation and patient’s risk factors. Antiplatelet agents such as hydroxyurea and anagrelide have been used with positive results, although side effects such as leukemic transformation and anemia have been reported respectively. In a situation where thrombocytosis is posing a threat to life, plasmapheresis can be utilized for rapid reduction.
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