Sarah Kerklap Posted Date May 5, 2022 5:30 AM Unread Mr. Dar

Sarah Kerklaposted Datemay 5 2022 530 Amunreadmr Darrin Lancaster

Describe a case of a 28-year-old male presenting with acute shortness of breath, pleuritic chest pain, and signs of pulmonary embolism (PE). Discuss the diagnostic steps taken, including laboratory tests and imaging modalities, and analyze the findings that support the diagnosis. Evaluate the role of familial and genetic factors, particularly protein C deficiency, in thrombotic risk. Explain the rationale for the chosen treatment approach and discuss potential management considerations for patients with hereditary hypercoagulable states, including the risks associated with anticoagulation therapy.

Paper For Above instruction

Introduction

The presentation of acute shortness of breath accompanied by pleuritic chest pain in young adults is a critical clinical scenario requiring rapid and accurate diagnosis to prevent morbidity and mortality. Pulmonary embolism (PE) remains a life-threatening condition that often demands a multi-modal approach integrating clinical assessment, laboratory testing, and imaging studies. This paper explores a case involving a 28-year-old male with signs consistent with PE, highlighting the diagnostic process, the significance of genetic predispositions such as protein C deficiency, and considerations for management strategies tailored to hereditary hypercoagulable states.

Clinical Presentation and Initial Assessment

The patient, a young male with no significant past medical history apart from renal calculi two years earlier, presented with a two-hour history of acute dyspnea and cough, with symptoms worsened by coughing and deep breathing. He also experienced pleuritic chest pain—a classic symptom associated with PE. Family history revealed premature cardiovascular disease, which raised suspicion of a possible hereditary component. On physical exam, vital signs were notable for tachycardia, and laboratory tests showed leukocytosis, negative troponin, and an elevated D-dimer, which is a sensitive marker for thrombotic activity but lacks specificity.

Diagnostic Imaging and Laboratory Evaluation

The initial imaging modality was a chest X-ray that demonstrated blunting of the right costophrenic angle, suggestive of pleural effusion, although this is not pathognomonic for PE. Recognizing the limitations of chest radiographs in diagnosing PE, the clinician opted for a computed tomography angiography (CTA), regarded as the gold standard in PE diagnosis. The CTA revealed intra-arterial filling defects in multiple vessels and segmental consolidation in the right lower lobe, confirming the presence of thrombi obstructing pulmonary arteries.

Further evaluation involved ultrasonographic assessment of the lower extremities, which revealed thrombus formation in the right common iliac and femoral veins—an indication of deep vein thrombosis (DVT), often the source of emboli. The pathophysiology is explained by Virchow’s triad: venous stasis, endothelial injury, and hypercoagulability. In this case, the absence of other risk factors such as prolonged immobility or obesity shifted focus toward hereditary causes.

Genetic Predisposition and Thrombophilia Testing

Given the family history and no apparent acquired risk factors, thrombophilia screening was performed, revealing a significant deficiency in protein C, with a level of 40%. Protein C is a vitamin K-dependent anticoagulant that regulates clot formation by inactivating factors Va and VIIIa. Deficiency predisposes individuals to thrombotic events, especially in hereditary forms, which tend to present at younger ages and may be unprovoked. The diagnosis points towards a genetic mutation rather than an acquired deficiency, and family members should be considered for screening.

Role of Cardiac Evaluation

An electrocardiogram (EKG) showed tachycardia with premature atrial complexes (PACs) but no signs of right ventricular strain, which is often seen in PE. Troponin testing was negative, indicating no concurrent myocardial injury. An echocardiogram failed to reveal right ventricular dilation or dysfunction, suggesting the PE was not causing significant right heart strain at the time of assessment. These findings influence prognosis and management decisions.

Management Considerations

The presence of hereditary protein C deficiency complicates anticoagulation therapy, notably with warfarin, due to its transient prothrombotic effect during initiation. Warfarin inhibits vitamin K-dependent coagulation factors, including protein C, leading to an initial hypercoagulable state and increased risk for skin necrosis in these patients—a potentially fatal complication. Therefore, alternative anticoagulants such as low-molecular-weight heparin are often preferred initially, with a transition to oral anticoagulants after stabilization.

Long-term management generally involves indefinite anticoagulation to prevent recurrent thromboembolic events, especially because of the unprovoked nature of the initial PE associated with hereditary thrombophilia. The decision for lifelong therapy must balance re-thrombosis risk against bleeding complications, with direct oral anticoagulants (DOACs) providing a favorable safety profile over vitamin K antagonists for many patients.

Genetic Counseling and Family Screening

In light of the hereditary aspect, testing first-degree relatives for protein C deficiency is recommended. Genetic counseling assists affected families in understanding their risks and managing preventive measures. Lifestyle modifications, avoiding estrogen-containing medications, and prompt treatment of minor infections or injuries are essential components of risk reduction.

Conclusion

This case underscores the importance of a comprehensive approach to suspected PE, incorporating clinical suspicion, targeted laboratory testing, and advanced imaging. Hereditary deficiencies such as protein C deficiency significantly contribute to thrombotic risk in young adults and necessitate tailored anticoagulation strategies. Early recognition, appropriate management, and genetic counseling are vital to prevent recurrent events and improve outcomes in patients with inherited thrombophilias.

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