Indian Journal of Pathology and Microbiology

CASE REPORT
Year
: 2018  |  Volume : 61  |  Issue : 1  |  Page : 116--119

Autopsy findings in an atypical case of occult massive fatal pulmonary embolism in a backdrop of hyperhomocysteinemia


Pratibha Misra1, Arijit Kumar Ghosh2, Aneeta Jassar1,  
1 Department of Pathology and Laboratory Medicine, Military Hospital, Jalandhar, Punjab, India
2 Department of Medicine and Cardiology, Military Hospital, Jalandhar, Punjab, India

Correspondence Address:
Aneeta Jassar
Department of Pathology, Military Hospital, Jalandhar - 144 005, Punjab
India

Abstract

A 43-year-old apparently healthy male presented with fever and presyncope. He was suspected to have massive pulmonary thromboembolism based on the clinico-biochemical profile. Despite aggressive thrombolytic therapy, he succumbed to his illness within 12 h of admission. Postmortem examination showed massive pulmonary thromboembolism and hyperhomocysteinemia with low high-density lipoproteins (HDL) cholesterol with antemortem blood sample. Herein, we report autopsy findings in a rare case of a young male with occult massive pulmonary thromboembolism without deep vein thrombosis, who had an atypical clinical presentation and was found to have underlying hyperhomocysteinemia and decreased HDLc. An acute, massive PE can present a diagnostic challenge due to the rate and severity of decompensation seen in afflicted patients. A high index of suspicion is required for early detection of pulmonary embolism in a young patient with atypical presentation and without obvious risk factors.



How to cite this article:
Misra P, Ghosh AK, Jassar A. Autopsy findings in an atypical case of occult massive fatal pulmonary embolism in a backdrop of hyperhomocysteinemia.Indian J Pathol Microbiol 2018;61:116-119


How to cite this URL:
Misra P, Ghosh AK, Jassar A. Autopsy findings in an atypical case of occult massive fatal pulmonary embolism in a backdrop of hyperhomocysteinemia. Indian J Pathol Microbiol [serial online] 2018 [cited 2022 Oct 4 ];61:116-119
Available from: https://www.ijpmonline.org/text.asp?2018/61/1/116/228160


Full Text



 Introduction



Pulmonary thromboembolism is one of the spectrums of manifestations of venous thromboembolism (VTE). It has a plethora of predisposing factors, both congenital and acquired. A large acute pulmonary embolism (PE) is usually a catastrophic consequence of deep vein thrombosis (DVT). It has been estimated that 1% of all patients admitted to hospitals die of acute PE, and 10% of all hospital deaths are PE-related.[1] Among patients with higher severity of disease, in-hospital mortality approaches 50%.[2] Massive occult PE in the absence of underlying DVT and in a completely asymptomatic individual, leading to a fatal outcome, is rare. Herein, we report autopsy findings in a case of fatal occult massive PTE detected to have hyperhomocysteinemia and low high-density lipoproteins (HDL) cholesterol when tested on the antemortem sample.

 Case Report



A 43-year-old apparently healthy male nonsmoker with no known comorbidities presented with 9 days' history of low-grade fever on and off, associated with easy fatigability, and one episode of presyncope. On admission, he had tachycardia (heart rate 98/min), and systemic examination was unremarkable. However, within a few hours of admission, he developed sudden hypotension, tachypnea, and hypoxemia.

His electrocardiography (ECG) showed sinus tachycardia, S1Q3T3 pattern with T-wave inversion in V1-4 and chest X-ray was suggestive of pulmonary thromboembolism [Figure 1]. His D-dimer was raised [Table 1]. Based on the clinical features and investigations, he was suspected to have pulmonary thromboembolism and managed aggressively for the same. However, he suffered a cardiac arrest within 12 h of admission and despite resuscitative efforts with fluids, inotropes, and cardiopulmonary resuscitation, he could not be revived and eventually succumbed to his illness.{Figure 1}{Table 1}

Postmortem investigations carried out on antemortem samples revealed homocysteine levels of 27 μmol/L (normal: 3.7–13.9 μmol/L) by high-performance liquid chromatography (HPLC). Serum Vitamin B12/folic acid levels and the rest of the procoagulation profile workup (protein S, protein C activity, lupus anticoagulant, antiphospholipid level antibodies, and antithrombin activity) were normal.

Pathological findings on autopsy

Gross findings

Heart – the right atrium showed thrombus [Figure 2]a. Ventricle wall thickness was normal and all coronaries were patent. Both the lungs were edematous. Right pulmonary artery, when cut open at the bifurcation, showed a large blood clot [Figure 2]b extending as occlusive laminated embolus blocking the lumen of the right pulmonary artery and extending into the right lung [Figure 2]c. The pulmonary artery tree was dissected from the hilum toward the periphery along its branches and revealed emboli extending along its entire length and subdivisions. Transverse sections of the right lung parenchyma revealed emboli in small peripheral vessels [Figure 2]d. No gross infarction of lung parenchyma was seen. Other systems were unremarkable, and there was no evidence of thrombosis in the leg veins.{Figure 2}

Histopathological features

Histological examination confirmed massive thromboembolic obstruction of the pulmonary artery and its branches [Figure 3]a. Multiple sections from the emboli of pulmonary artery showed laminations (Lines of Zahn) with alternate pale layers of platelets admixed with fibrin and darker layers containing red cells [Figure 3]b. Histological evidence of organization of thrombus in the form of the presence of fibroblasts and collagen with fibrin attachment to underlying vessel wall was also noted [Figure 3]c. Left pulmonary vasculature showed no thrombus. The right and left lung parenchyma showed alveolar edema [Figure 3]d.{Figure 3}

 Discussion



VTE is a disease with a spectrum of manifestations that include thrombophlebitis, DVT, and PE. Most pulmonary emboli have their origin in clots in the iliac, deep femoral, or popliteal veins. However, in many instances of PE, no peripheral source of thrombosis is ever identified.[3] Despite the clinical significance of risk factors for VTE, Morgenthaler and Ryu [4] found that 12% (11 of 92) of patients with PE as the cause of death at autopsy lacked any known risk factor. The exact rate of asymptomatic PE in the general population or in patients with occult DVT is unknown. It is possible that healthy individuals frequently have small emboli that dissolve rapidly and never become symptomatic.[3] Our case was a young physically active male who had been asymptomatic to date and had had no history of thromboembolism in the past.

The presentation of PE is occasionally dramatic, but more commonly patients present with subtle clinical findings, or they may be completely asymptomatic. The classic findings of hemoptysis, dyspnea, and chest pain are insensitive and nonspecific for a diagnosis of PE, with fewer than 20% having this classic triad.[3] Even unexplained dyspnea, which is a single historical finding most sensitive for PE was absent in 8% of the patients studied.[5] Our case lacked classical symptoms of hemoptysis, dyspnea, and chest pain.

Atypical presentations of PE are common, with symptoms such as abdominal pain, back pain, fever, cough, atrial fibrillation, and hiccoughs.[6]Occult PEs are known to exist in asymptomatic patients in high-risk groups. Syncope is present in 8%–13% of all patients with PE and is secondary to right ventricular outflow obstruction causing transient hypotension leading to presyncope/syncope.[7] In a study of 92 patients at autopsy with PE as the cause of death, more than one quarter had a history of syncope.[4] Patients with PE who present with syncope carry a worse prognosis than patients who do not.[7] Our patient gave a history of one episode of presyncope before the day of admission.

PE as a clinical entity often presents as a rapid and severe hemodynamic collapse leaving clinicians with little time to react. Our patient suffered hemodynamic instability, poor contractility, and eventually cardiac arrest, which correlated with high brain natriuretic peptide levels and a large clot found in the right atrium on autopsy. Among available diagnostic modalities, ECG, arterial blood gas analysis, chest X-ray, and D-dimer all have a limited role in the evaluation of PE. The primary utility of the ECG is its ability to point to an alternate diagnosis, such as acute coronary syndrome or pericarditis.[3] The most common ECG abnormality, found in 68%, is T-wave inversion in the precordial leads.[6]

As the autopsy confirmed massive PE and the individual had no apparent risk factors, his antemortem blood sample was tested for hyperhomocysteine, protein C, protein S, anti-thrombin, and Factor V Leiden to look for congenital prothrombotic states. Our case had mildly elevated homocysteine level of 27 μmol/L by HPLC and low-HDL cholesterol (HDLc) of 29 mg/dL. Hyperhomocysteinemia is known to cause thrombosis through endothelial dysfunction, reduced nitric-oxide bioavailability, impaired endothelium-dependent vasodilatation, augmentation of the recruitment and adhesion of circulating mononuclear cells to the endothelium, inhibition of endothelial cell antithrombotic properties, and promotion of atherosclerosis.[8] Our case is unusual in presentation as he had no history of thromboembolic disease and acute PE was the first apparent manifestation of hyperhomocysteinemia. A similar case of unprovoked PTE found to have hyperhomocysteinemia as the only predisposing factor was reported by Kariyappa et al. However, their case was thrombolyzed successfully with streptokinase followed by heparin.[9]

In their study Karalezli et al. found significantly lower levels of HDLc in patients with PE as compared to the control group and significantly low levels of HDLc in patients with high homocysteine levels in the PE group. This led them to propose that low-HDLc level with hyperhomocysteinemia increased susceptibility to PE.[10]Our case was found to have low levels of HDLc which could have aggravated the prothrombotic risk of hyperhomocysteinemia.

A review of recent literature reveals little more than four autopsy series covering PE over the last 30 years. In a 10-year autopsy study, Sweet et al. identified PE as the mechanism of death in 108 of 982 cases (11%, 95% CI 9.01–12.99%).[11] Typically, adherent emboli bulge from the incised pulmonary arteries and transverse incisions of the pulmonary parenchyma may disclose emboli in the small peripheral vessels, which tend to protrude above the cut surface. The pathologic criteria used to determine acute PE include (1) gross evidence of an occlusive thrombus in the bifurcation of the pulmonary artery and (2) histologic evidence that this lesion is both organizing and associated with the vessel wall, that is, fibrin attachment to underlying vessel wall, organization with or without early recanalization, and fibrin lamination (Lines of Zahn).[11] All these features were demonstrated on autopsy in our case. A 24-year autopsy study showed involvement of segmental or subsegmental pulmonary arteries in most of the cases (72.4%) of nonfatal PTE, while thrombi in the main arteries, as well as in arteries of the trunk and above, were more prevalent in fatal PTE. The same study found that thrombi from the right heart chambers and pelvic veins were associated with fatal PTE, whereas thrombi from lower limbs and undetermined sites were associated with nonfatal PTE.[12] Free thrombi in the right heart chambers are rare and are usually revealed when patients with suspected or confirmed PTE are submitted to echocardiography. These thrombi may serve to identify patients at risk for dying from recurring VTE.[11] The case presented had a large thrombus in the right atrium, and this was the likely cause of the fatal PE.

 Conclusion



We have presented autopsy findings in a fatal case of massive PE who had no apparent risk factors, an acute atypical presentation and a stormy course in hospital. Investigations on antemortem sample revealed hyperhomocysteinemia and low HDLc which probably had a synergistic prothrombotic effect. As acquired causes of hyperhomocysteinemia were ruled out in this case, the cause of hyperhomocysteinemia was most likely genetic. However, mutational analysis for MTHFR and cystathionine-B-reductase could not be carried out. This case also highlights the importance of assessment of homocysteine levels in all patients presenting with PE, especially in younger individuals who have no apparent risk factors for VTE.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Lankeit M, Konstantinides S. Mortality risk assessment and the role of thrombolysis in pulmonary embolism. Crit Care Clin 2011;27:953-67, vii-viii.
2Choi WH, Kwon SU, Jwa YJ, Kim JA, Choi YH, Chang JH, et al. The pulmonary embolism severity index in predicting the prognosis of patients with pulmonary embolism. Korean J Intern Med 2009;24:123-7.
3Laack TA, Goyal DG. Pulmonary embolism: An unsuspected killer. Emerg Med Clin North Am 2004;22:961-83.
4Morgenthaler TI, Ryu JH. Clinical characteristics of fatal pulmonary embolism in a referral hospital. Mayo Clin Proc 1995;70:417-24.
5Susec O Jr., Boudrow D, Kline JA. The clinical features of acute pulmonary embolism in ambulatory patients. Acad Emerg Med 1997;4:891-7.
6Feied CF. Venous thrombosis and pulmonary embolism. In: Marx JA, Hockberger RS, Walls RM, Adams J, Barkin RM, Barsan WG, et al., editors. Rosen's Emergency Medicine Concepts and Clinical Practice. 5th ed. Atlanta: Mosby; 2002. p. 1210-34.
7Brilakis ES, Tajik AJ 82-year-old man with recurrent syncope. Mayo Clin Proc 1999;74:609-12.
8Hainaut P, Jaumotte C, Verhelst D, Wallemacq P, Gala JL, Lavenne E, et al. Hyperhomocysteinemia and venous thromboembolism: A risk factor more prevalent in the elderly and in idiopathic cases. Thromb Res 2002;106:121-5.
9Kariyappa M, Agrawal N, Somanna S, Prakash SS, Veerappa K, Nanjappa MC. Unprovoked pulmonary thromboembolism predisposed by hyperhomocysteinemia. J Ind Coll Cardiol 2014;4:239-42.
10Karalezli A, Parlak ES, Kanbay A, Senturk A, Hasanoglu HC. Homocysteine and serum-lipid levels in pulmonary embolism. Clin Appl Thromb Hemost 2011;17:E186-9.
11Sweet PH 3rd, Armstrong T, Chen J, Masliah E, Witucki P. Fatal pulmonary embolism update: 10 years of autopsy experience at an academic medical center. JRSM Short Rep 2013;4:2042533313489824.
12Bok Yoo HH, Mendes FG, Alem CE, Fabro AT, Corrente JE, Queluz TT. Clinicopathological findings in pulmonary thromboembolism: A 24-year autopsy study. J Bras De Pneumol 2004;30:426-32.