Hypercoagulable State Leading to Paraplegia in a Middle-Aged Man

Abstract

A 37-year-old man presented with an unusual thrombotic disorder characterized by acute paraplegia and the absence of palpable pulses due to extensive arterial thrombosis of the aorta and its distal branches. The patient had an extremely complicated course that necessitated multiple revascularization procedures over a 1.5-year period. This case is unusual not only because of its complexity but also because of the patient's relatively young age, his lack of risk factors for vascular disease, and the presence of a neurologic deficit that improved when circulation was restored. More unusual, however, is the fact that all diagnoses were excluded except for a high lipoprotein(a) level. To our knowledge, this is the 1st reported case in which aortic thrombosis has been related to hypercoagulability. (Tex Heart Inst J 2002;29:30–2)

The clotting cascade is responsible for many challenging cases encountered by cardiovascular surgeons. Historically, isolated case reports have described painless paraplegia resulting from conditions such as abdominal aortitis; ¹ aortic thrombosis; ^2–4 large-vessel thrombosis related to essential thrombocytosis; ⁵ and acute abdominal aortic occlusion related to atherosclerosis, dissection, or trauma. ⁶

We report the case of a middle-aged man who presented with paraplegia related to aortoiliac thrombosis and who, after undergoing vascular repair, had many recurrent thrombotic episodes. His disease was attributed to a hypercoagulable state—a high lipoprotein(a) or Lp(a) level—which, to our knowledge, has not previously been reported as a cause of aortic thrombosis.

Case Report

On 19 May 1999, a 37-year-old black man presented at our emergency department with lower back pain and paraplegia. Three months earlier, working as a technician for a lighting company, he had twisted his back while on a ladder. He had no history of diabetes or hypertension but was an occasional smoker. ⁷ His father had experienced a cerebrovascular accident from which he had fully recovered.

The clinical examination revealed a sturdy, middle-aged man whose lower back was tender. A straight-leg-raising (SLR) test yielded a positive result at 45° on the right side. The patient felt as though his legs were ice cold; otherwise, sensation was reduced in both legs and feet. He was paraplegic, with a loss of motor function from the waist downward. The femoral, popliteal, and pedal pulses were not palpable bilaterally. An arterial Doppler echocardiographic examination revealed complete iliac occlusion. The external iliac, common femoral, superficial femoral, profunda femoris, popliteal, peroneal, and anterior and posterior tibial arteries were also completely occluded. There was no demonstrable blood flow in either great toe. Aortography showed that the abdominal aorta was abruptly occluded just distal to the renal arteries.

The patient was taken to the operating room the same day, where he underwent urgent extensive bilateral thrombectomies, bilateral aorto–femoral bypass grafting, right femoro–peroneal bypass grafting with a GORE-TEX® vascular graft (W.L. Gore & Associates, Inc.; Flagstaff, Ariz), and interposition of a saphenous vein graft from the GORE-TEX graft to the right posterior tibial artery.

Pathologic examination of a left-popliteal-artery specimen revealed organizing thrombus and medial calcification. ⁸ Laboratory markers for assessing hypercoagulable states ^9,10 suggested a clotting factor deficiency and the absence of a circulating anticoagulant. The patient's Lp(a) level was 72 mg/dL (normal value for black men, <54 mg/dL). The protein C and S levels were within normal limits, as were the antithrombin III and factor V Leiden levels.

The patient had an eventful postoperative course. Just 1 day after the initial placement of the vascular grafts, the patient underwent a thrombectomy and revision of a clotted femoro–peroneal graft. Five days later, he required a fasciotomy and débridement of the right leg. On 27 May, he developed acute renal failure and rhabdomyolysis, which resolved with conservative treatment. On 1 June, the patient underwent débridement of the left calf, followed 2 weeks later by skin grafting of the leg wounds. On 30 June, he was discharged from the hospital after a stay of 6 weeks. He had regained his lower-extremity motor and sensory function completely.

On 28 September 1999, the patient again presented at our institution with ischemia in the left lower extremity. He was given an intra-arterial infusion of tissue plasminogen activator and was discharged from the hospital on warfarin therapy. On 22 November, the patient returned for débridement of an infected neurotropic ulcer near the 5th toe of his right foot. Despite antibiotic therapy and local wound care for the next 6 weeks, his right foot became gangrenous; amputation above the right knee was performed on 19 January 2000. Less than 3 months later (3 April), the amputation stump became infected and had to be revised.

On 18 June 2000, the patient again presented with left lower-limb ischemia, and he underwent thrombectomy of the aorto–femoral bypass graft and the left profunda femoris artery. In addition, on the basis of an intraoperative angiogram, a left femoro–posterior tibial bypass was performed with a nonreversed composite saphenous vein graft. Two weeks later (3 July), a left femoro–anterior tibial bypass was performed with use of a left forearm vein. On 21 July, the patient was discharged from the hospital on a regimen of baby aspirin (81 mg daily), warfarin, and physical therapy.

On 24 October 2000, the patient received a right above-the-knee prosthesis. On 6 December, he was readmitted for leg pain. Angiography revealed occlusion of the left limb of the aorto–femoral graft, collateral filling of the left femoro–posterior tibial graft, and high-grade stenosis at the peroneal–posterior tibial anastomosis. The prothrombin time was 16.8 seconds and the international normalized ratio (INR) was 1.8. The next day, the patient was taken to the operating room, where the occluded grafts were replaced with left femoro–anterior tibial and composite tibial–peroneal GORE-TEX bypass grafts. He recovered uneventfully. When seen at the 2-year follow-up visit in May of 2001, the patient was able to walk with his right above-knee prosthesis, and he was taking baby aspirin, warfarin, and clopidogrel regularly.

Discussion

Although the English medical literature contains isolated reports of cases similar to ours, none has involved exactly the same clinical presentation, pathogenesis, and recurrent extensive disease. In our patient, there was no apparent reason for the occlusion shown by angiography (Fig. 1). We proposed a number of differential diagnoses, including Buerger's disease, atherosclerosis, and hypercoagulability. All diagnoses were excluded except for a high Lp(a) level, which has not previously been recognized as a cause of aortic thrombosis. Levels of Lp(a) are largely genetically determined. Higher levels of Lp(a) are found in black than in white persons, and higher levels are also present in women than in men. In white patients, an Lp(a) level of 30 mg/dL or more has been established as a risk threshold for the development of coronary, cerebral, and peripheral atherosclerosis. By means of a linear logistic relationship, Lp(a) has been related to the risk of premature peripheral vascular disease. ¹¹

Fig. 1 Aortogram showing total occlusion of the aorta below the renal arteries.

Elevated Lp(a) levels present an increased risk of coronary and cerebral thrombotic events. Several prospective studies, including the Helsinki Heart Study, ¹² Lipid Research Clinics Coronary Primary Prevention Trial, ^13,14 British United Provident Association Study, ¹⁵ and Quebec Cardiovascular Study, ¹⁶ have shown conflicting results regarding the relationship between elevated Lp(a) levels and coronary thrombosis. This paradox may be attributable, in part, to the fact that most myocardial infarctions occur in individuals with normal Lp(a) levels. There is a rightward skew of the distribution curve for Lp(a), and increased risk of myocardial infarction is probably limited to persons with the highest levels of Lp(a). ¹¹

More than one hypothesis has been proposed to explain the relationship between Lp(a) and vascular damage. The plasminogen inhibitor hypothesis is built on the fact that Lp(a) is structurally homologous to plasminogen. Lipoprotein(a) is thought to exert an inhibitory influence on the fibrinolytic system by competing with the binding of plasminogen to endothelial cells, which leads to prolonged intimal damage and local thrombus formation. According to the cholesterol-targeting hypothesis, Lp(a) has an important physiologic effect because of its low-density lipoprotein moiety. By binding to plasminogen receptors at sites of endothelial injury, Lp(a) targets the delivery of cholesterol to areas of rapid cell growth. Abnormally high plasma levels of Lp(a) lead to excess cholesterol deposition at sites of vascular wall injury, predisposing these vessels to plaque formation. ¹⁷

In our patient, the severely diseased large- and medium-sized vessels warranted multiple revascularization procedures, followed by postoperative anticoagulation and close observation. Because the patient's paraplegia resolved and lower-limb sensation returned completely, we determined vascular occlusion to be the cause of his neurologic symptoms. Presumably, the artery of Adamkiewicz was involved, since the patient recovered his motor and sensory function after undergoing the thrombectomy and revascularization procedures.

This case is unique because the patient was relatively young, was nonhyperlipidemic, and lacked a family history of vascular disease. In addition, his vascular disease was unusually recurrent and extensive, which required the care of many specialists and necessitated several complex surgical procedures. Moreover, the patient had a temporary neurologic deficit due to ischemia, which was surgically correctable. The assistance of various specialists was valuable for supplementing surgical management in this complicated case involving multiple organ systems.

Acknowledgment

We thank Shirley A. Riggs, MD, consulting hematologist, and Zvonimir Krajcer, MD, of the Peripheral Vascular Disease Service, for their assistance with this case.