Acute Myocardial Infarction in a 19-Year-Old Female Owing to Hypercoagulable State of Pregnancy and the Puerperium
- Volume 20 - Issue 9 - September, 2008
- Posted on: 10/29/08
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From the Division of Cardiology, Department of Medicine, University of Louisville, Louisville, Kentucky.
The authors report no conflicts of interest regarding the content herein.
Manuscript submitted February 4, 2008, provisional acceptance given April 14, 2008, and accepted April 16, 2008.
Address for correspondence: Buddhadeb Dawn, MD, Division of Cardiology, 550 S Jackson St. ACB 3rd Floor, University of Louisville, Louisville, KY 40292. E-mail: [email protected]
ABSTRACT: A well-recognized, yet rare, complication of pregnancy is acute myocardial infarction (AMI). In some cases, the hypercoagulable state associated with pregnancy has been the primary contributor to coronary artery thrombosis. However, we describe a clinical presentation of an AMI occurring in a 19-year-old with no traditional cardiac risk factors, not during pregnancy, but in the puerperium.
J INVASIVE CARDIOL 2008;20:E262–E264
The incidence of acute myocardial infarction (AMI) associated with pregnancy is approximately 3–10 cases per 100,000 deliveries, and is highest in multigravidas older than 33 years of age, during the third trimester of either their first or second pregnancy.1 The strongest independent predictors of infarction are traditional cardiovascular risk factors, namely hypertension, diabetes and smoking.1,2 However, in almost 26% of patients with pregnancy-related AMI, an underlying acquired (antiphospholipid antibody syndrome and hyperhomocystinemia) or inherited (antithrombin III, protein C, protein S, and factor V Leiden) thrombophilia acts as the primary contributor to the development of acute coronary artery thrombosis.1,2 Although the majority of pregnancy-related AMIs do occur during pregnancy, approximately 27% occur in the puerperium (the period immediately following delivery that extends 6–8 weeks postpartum).1,2 Of the latter, approximately 21% of these patients present with isolated thrombi in the absence of coronary artery disease.2
We describe a 19-year-old patient with early presentation of a non-ST-elevation AMI (NSTEMI) secondary to in situ coronary thrombosis without atherosclerotic disease, and with neither traditional risk factors nor underlying known thrombophilia.
Case Report. A 19-year-old African-American female (para 1011) with recently diagnosed peripartum cardiomyopathy and no traditional cardiac risk factors was admitted on day 33 postpartum of a spontaneous vaginal delivery with unstable angina of approximately 60 minutes duration. Her electrocardiogram revealed new symmetric T-wave inversions in leads V5–6, I and aVL. The creatine phosphokinase-MB level was 210 UI/mL (normal range, 0 to 25 UI/mL) and the cardiac troponin T level was 3.65 µg/L (normal, < 0.01 µg/L). The patient received a 325 mg loading dose of aspirin (chewed), a 600 mg loading dose of clopidogrel and a 4,000 U bolus of unfractionated heparin, which was maintained as a continuous intravenous infusion at 12 U/kg/hour. Her coronary angiogram (Figure 1) revealed two discrete intracoronary thrombi with subtotal occlusions: (i) in the distal portion of the left circumflex artery (LCX); and (ii) in the large second obtuse marginal (arrowheads); both with TIMI grade I flow. No thrombus was observed in the left anterior descending or the right coronary artery (not shown). A 6 Fr Judkins left 4 (JL4) catheter was used to selectively engage the left main coronary artery and intracoronary infusion of abciximab was performed. After 20 minutes, coronary flow improved to TIMI grade III in both branches of the LCX artery. Her angina resolved and the ischemic ECG changes completely resolved. Subsequently, a follow-up coronary angiography and intravascular ultrasound (IVUS) examination was performed, revealing resolution of thrombi with no evidence of ruptured atherosclerotic plaques or existent atherosclerotic disease. Transthoracic as well as transesophageal echocardiography revealed globally depressed LV function and apical hypokinesis but no valvular or mural thrombi (Figure 2). An extensive serologic workup for genetic and acquired thrombophilia was negative (Table 1).
Discussion. The “hypercoagulable state of pregnancy” is considered an independent risk factor for the development of acute coronary syndromes. In the absence of traditional risk factors and/or thrombophilia, this hypercoagulability is believed to be responsible for the development of AMI, especially during the third trimester, and in the puerperium.1,2 Unlike other acquired thrombophilias, pregnancy-related hypercoagulability is temporary (occurring only in the peripartum period and puerperium), and results from disruption of homeostasis and profound dysregulation in the activity of the intrinsic and extrinsic coagulation system. Biochemically, it is characterized by: (i) a decreased production of releasable tissue plasminogen activator (t-PA); (ii) an increase in fast-acting t-PA inhibitor; and (iii) is often associated with alterations in the activity and/or levels of endogenous anticoagulants such as protein S and activated protein C3-5. The net result is procoagulant activity that peaks around term and extends 6–8 weeks postpartum. Typical laboratory findings include increased plasma concentrations of D-dimer and fibrinogen, as well as increased prothrombin and thrombin times (Table 1).2–4 Although the natural history of this entity is quite variable, AMI owing to pregnancy-related hypercoagulability is diagnosed clinically by the presence of these laboratory data and, most importantly, by the exclusion of any underlying thrombophilia, coronary vessel disease or upstream thromboembolic sources. Nevertheless, as no decisive pathognomonic evidence exists to permit a specific diagnosis in these particular cases, the basis for the cascade of events leading to the intracoronary thrombi observed in our patient had to be inferred.
The most common reported mechanism for AMI in the peripartum period is coronary atheromatous plaque disruption and subsequent acute coronary thrombosis.1,2,6 However, in the pueperium, spontaneous coronary dissection and presumed coronary vasospasm, respectively, account for the majority of infarctions. Regarding the latter, one study looking at the cause of AMI in the pueperium found that 50% of these patients had no evidence of atheromatous plaque burden; however, of these, 21% had in situ coronary thrombi.2 In such cases, acute in situ coronary thrombosis and concomitant coronary vasospasm is the proposed mechanism inciting infarction.1,2
Accordingly, in the absence of known cardiovascular risk factors or underlying thrombophilia, it is most likely that our patient’s AMI occurred as a result of in situ coronary thrombosis secondary to the “hypercoagulable state” associated with pregnancy and the pueperium itself. Our diagnosis is further bolstered by follow-up angiography and IVUS examination verifying the absence of atherosclerotic disease. Moreover, no intracardiac mural or valvular thrombi were identified in our patient, despite its extremely rare occurrence even in the presence of severe left ventricular dysfunction,6 making it even more unlikely that the coronary thrombi described in this report were of thromboembolic origin. To our knowledge, there exist only a few case reports demonstrating pregnancy-related hypercoagulability as the sole etiology of AMI.
In these patients, the variable natural history of this clinical entity makes it very challenging to measure the efficacy of any intervention in such an uncontrolled setting, and, thus, even more difficult to formulate specific evidence-based treatment recommendations. Nevertheless, in the absence of randomized, controlled trials to guide the treatment of unique patients such as ours (with multiple intracoronary thrombi and no evidence of atherosclerotic disease), in this particular case, reperfusion therapy appeared to be appropriate. We were able to achieve successful reperfusion via local delivery of the glycoprotein IIb/IIIa inhibitor abciximab. Our approach was based on the documented clot-dissolving properties of these agents in the setting of fresh or ongoing thrombosis.7 Reestablishment of TIMI grade III flow in both vessels in our patient does suggest a role for this treatment in similar patients, as well as in patients at risk of undergoing more aggressive strategies. At discharge, however, patients such as ours are typically transitioned to aspirin and warfarin, to be continued for 3–6 months as recurrent arterial thrombosis is still a continuing risk.2 Our patient was discharged home on warfarin and aspirin therapy. A repeat echocardiogram was performed after 3 months and revealed reduced, yet persistent, biventricular chamber dilatation, moderately improved, though still depressed, biventricular function and still no evidence of intracardiac thrombi. After 6 months, our patient was lost to follow up, but had no recurrence of chest pain during this time.
This case underscores the importance of suspecting pregnancy-related hypercoagulability as the etiology of AMI, not only during pregnancy, but also well into the puerperium. Furthermore, although management decisions in these very challenging cases must be made in accordance with the unique circumstances surrounding them, here we were able to report a positive outcome and demonstrate some efficacy for abciximab-based reperfusion therapy (and continued anticoagulation) in patients where pregnancy-related hypercoagulability is suspected. Nevertheless, a search for other identifiable and treatable contributors must be undertaken before making such a diagnosis, as treatment modalities will likely vary.