Acute Thrombotic Thrombocytopenic Purpura Following Orthopedic Surgery: Case Report and Review of the Literature

Abstract

Thrombotic thrombocytopenic purpura (TTP) is an uncommon cause of hematological and renal abnormalities in the postoperative period. An association between TTP and orthopedic surgery, a rare entity, has been reported in the literature. It has the strong possibility of being fatal and therefore should be treated immediately, mostly by plasmapheresis. We report a 15-year-old girl of TTP following a high tibial valgus osteotomy (HTO).

• thrombotic
• thrombocytopenic purpura
• orthopedic surgery
• postoperative
• renal failure

INTRODUCTION

Thrombotic thrombocytopenic purpura (TTP) as a microangiopathic hemolytic anemia (MAHA) was characterized by Moschowitz in 1925.¹ TTP was subsequently redefined as a pentad of thrombocytopenia, MAHA, renal impairment, fever, and mental state changes.² TTP is a life-threatening disorder that can be either congenital or acquired. Acquired causes of TTP can be listed as acute idiopathic (reduced ADAMTS13 activity), drugs (oral contraceptives, cyclosporin, quinine, mitomycin C, and ticlopidine), autoimmune disease (systemic lupus erythematosus), malignancy, surgery, bone marrow transplantation, pregnancy, and infection [human immunodeficiency virus (HIV), Escherichia coli 0157].¹

The occurrence of TTP after surgery is a rare clinical syndrome with considerable similarity to classic TTP in presentation. TTP has been described following vascular surgery,^3,4 coronary artery bypass grafting,^3,5 orthopedic surgery,^6,7 transurethral resection of the prostate,¹ abdominal surgeries,^8–10 and gynecologic cancer surgery.¹¹

In this case report, we are going to discuss the possible reasons that are thought to attribute for the development of postoperative TTP, review the literature, and emphasize those cases to open the gates for early diagnoses and treatment.

CASE

A 15-year-old girl with cerebral palsy and genu valgum underwent surgery under general anesthesia. A lateral closing wedge valgus HTO was performed without any perioperative or acute postoperative complication. The patient had antibiotics (ampicillin sulbactam) for infection prophylaxis (1 dose preoperative and for 24 h postoperative). Before surgery the patient was apparently fit and well, taking no medication. On the second postoperative day, the patient suffered nausea, vomiting, reduction in the amount of urine, and lower extremity edema. She remained hemodynamically stable. Blood pressure was 100⁄60 mm Hg, heart rate 80 beats/min, oxygen saturation 98% on room air, temperature 36.7°C. She had not experienced any neurological changes. Examination of the cardiovascular, respiratory, and gastrointestinal systems was unremarkable, although oliguria and lower extremity edema were noted. On laboratory examination, preoperative full blood count, clotting, and urea and electrolytes were within normal limits [hemoglobin (Hb): 16.2 g/dL, white blood cells (WBC): 7000/mm³, platelets: 184,000/mm³, serum creatinine: 0.42 mg/dL], whereas on the second postoperative day the observations were Hb: 6.6 g/dL, WBC: 10,900/mm³, platelets: 23,000/mm³, serum creatinine: 4.74 mg/dL, urea: 110 mg/dL, lactate dehydrogenase (LDH): 1280 IU/L, potassium: 4.4 mmol/L.The coagulation mechanism tests were normal. Other examinations for virus contamination (e.g., HbsAg, HIV, etc.), direct versus indirect coombs, antinuclear antibody (ANA), and antineutrophil cytoplasmic antibody (ANCA) were negative; the others were as follows: C3: 94 mg/dL (16–38), C4: 13 mg/dL (16–38), fibrinogen: 181 mg/dL (180–350). Protein 500 mg/dL and 29 erythrocytes were found in automatic urine analysis. Urine microscopy revealed red cells with normal morphology. A 24-h urinary proteinuria was 2700 mg/day. Blood smear showed schistocytes. A recent ultrasound of the renal tract showed mild renal parenchymal echogenity. An assay for detecting an anti-vWF-cleaving enzyme antibody would have offered a diagnostic confirmation, but it was not available at the hospital. The laboratory results and the clinical image led to the diagnosis of TTP. Due to the critical situation, the patient immediately underwent exchange plasmapheresis. The treatment also involved oral prednisolone and aspirin. There was prompt improvement of thrombocytopenia, MAHA, and renal insufficiency. Following 14 exchange plasmapheresis all manifestations of TTP were completely resolved. Urine output was increased along with thrombocytes (200,000/mm³) and Hb (11.2 g/dL), whereas creatinine, urea, and LDH decreased (0.3 mg/dL, 25 mg/dL, and 218 IU/L, respectively). Because no schistocytes were seen on peripheral smear, the prednisolone therapy was gradually reduced and discontinued. The creatinine levels are still being followed within normal range (0.48 mg/dL) during postoperative 2 months.

DISCUSSION

TTP is defined as a process of platelet aggregation and thrombosis in the microvasculature which results in thrombocytopenia, hemolytic anemia, and organ ischemia. The underlying pathological process in TTP may compromise the function of any organ. Fever, neurologic abnormalities, and renal insufficiency may occur concurrently but are not required for the diagnosis.¹

Chang et al.⁹ described the first convincing association of TTP with surgery in a retrospective review of 15 years’ experience with TTP. Among 47 patients with TTP, 8 patients were diagnosed to have postoperative TTP, but none of them were found to have it after orthopedic surgery. Although postoperative TTP is most often after cardiac and vascular surgery, it can be seen after the other operations. In 1997, Robson et al.¹⁰ reported a case of postoperative TTP development after hemicolectomy for colonic carcinoma treatment. Postoperative TTP following gynecologic cancer surgery was seen in a patient who was diagnosed with metastatic poorly differentiated endometrial cancer.¹¹

TTP may develop secondary to many disorders but the reason for postoperative TTP is possibly due to endothelial damage.^3,12 TTP after endothelial injury has been recognized for more than 20 years. Surgical stress has been associated with TTP, probably by releasing massive amounts of unusually large von Willebrand factor (UlvWF) due to endothelial damage resulting from surgery in the setting of marginal levels of vWF-cleaving enzyme.¹² The deficiency of vWF-cleaving protease, which was designated ADAMTS 13, was charged responsible for the accumulation of UlvWF multimers in the plasma of patients with TTP.⁹

Diagnosis and treatment of postoperative TTP are often delayed because of confounding potential postoperative complications. The presence of postoperative thrombocytopenia, MAHA, fever, renal failure, and/or neurologic changes may be explained by the reasons such as heparin-induced thrombocytopenia (HIT) or other drug-induced thrombocytopenia, sepsis, disseminated intravascularly coagulation (DIC), complications of cardiac bypass, acute renal failure following cross-clamping of the aorta, large areas of denuded or damaged vascular endothelium, and operative or postoperative neurologic complications.¹³ TTP was therefore a diagnosis of exclusion. Although the early diagnosis of postoperative TTP is difficult, prompt treatment is of vital importance for the survival of the patients. Thus differential diagnosis must be done carefully. Characteristically, patients having a normal hemogram before surgery develop MAHA and consumptive thrombocytopenia 5–9 days following surgery with variable presence of fever, impaired renal function, and altered mental status. A helpful index may be an assay for detecting an anti-ADAMTS 13 autoantibody, but it is not available at many institutions.¹³

TTP development secondary to orthopedic surgery was first reported in the literature in 2002, following a total knee replacement surgery. But the authors were not sure whether TTP development was solely secondary to orthopedic surgery or was due to the prior use of ticlopidine.⁶ Another case of TTP development secondary to orthopedic surgery was reported in 2006.¹³ In this case the patient underwent a high tibial valgus osteotomy (HTO). Similarly in our case, TTP development was also secondary to an orthopedic operation that was performed for the correction of genu valgus deformity. To the best of our knowledge this is the third case report of TTP associated with orthopedic surgery. In our case there was no facilitating factor such as previous drug use or familial form of TTP. The early complaints of this patient were nonspecific such as nausea, vomiting, the mental status could not be evaluated well, because she had cerebral palsy, whereas the very first findings were related to renal system disorders like low urine output and edema over the lower extremities. Although in our case those early findings were related to renal system, this may not be true for all cases as a rule. After the development of TTP any organ system may be affected in any sequence regardless of the operation performed. According to the information obtained from previous records we can say that renal manifestations and neurologic disorders are important findings and may be alarming for the physicians who can be employed in the diagnosis of postoperative TTP development. Although postoperative acute renal failure occurs mostly due to hemorrhage, dehydration, and drug use for diagnosis and treatment, we must encounter possible postoperative TTP development as a rare reason that is curable if promptly diagnosed and treated.

TTP has the strong possibility of being fatal and thus should be treated immediately. Current approaches to management, such as using therapeutic plasma exchange, result in a survival rate of up to 80%.¹⁴ Plasma exchange should be initially performed daily until clinical manifestations improve. The platelet count and serum LDH (as an indicator of ongoing hemolysis) are useful markers of disease activity. Most patients require 5–10 daily plasma exchanges. Corticosteroids and antiplatelet agents are sometimes used as adjuvant treatments, but their contribution to overall benefit is uncertain. Platelet transfusions are not recommended as routine but should be considered to treat clinically serious bleeding.¹²

TTP should be considered in the differential diagnosis of unexplained thrombocytopenia and acute renal failure during postoperative period. Because TTP may develop after surgery in case of thrombocytopenia development during postoperative period, which cannot be linked to other known cause, physicians must keep this disorder in mind and begin the treatment immediately. We suggest that all surgeons should be aware of this because, although very rare, postsurgical TTP could be a life-threatening postoperative complication, which needs prompt diagnosis and treatment.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.