From the Department of Pediatrics, Institute of Medical Sciences, BHU, Varanasi, India.

Correspondence to: Dr. Rajniti Prasad, Department of Pediatrics, Institute of Medical Sciences, BHU, Varanasi, India. E-mail:[email protected]

Manuscript received: May 18, 2006; Initial review completed: October 6, 2006;
Revision accepted: August 1, 2006.

Abstract:

Deep vein thrombosis (DVT) in children is usually associated with inherited or acquired hypercoagulable state, mechanical obstruction, fractures of long bones, central venous catheterization and prolonged immobility. We report DVT in 4 children with culture proven staphylococcal septicemia. One child died, while other three survived with appropriate antibiotics and anticoagulation therapy.

Key words: Deep vein thrombosis (DVT), Staphylococcus aureus, Septicemia.

Deep vein thrombosis (DVT) is uncommon in children and its occurrence suggests an inherited or acquired hypercoagulable defect. There are few studies on DVT with Staphylococcus aureus septicemia in children(1,2). We report 4 children who developed DVT with fever, unilateral thigh swelling and rapid clinical deterioration, of which 3 recovered and one died due to pulmonary embolism.

Four boys, who were admitted in children ward with fever, cough, refusal to feed, swelling of lower limbs and single/multiple healing boils over body developed DVT. The baseline characteristics are mentioned in Table I. All children had swelling of thigh; 3 on right side and one on left side, positive Homan’s sign and difference of girth from joint line (knee) of more than 2.5 cm. Case no. 1 and 3 had clinical features suggestive of bronchopneumonia. Cardiac examinations in all patients were clinically normal. Liver and spleen were not enlarged.

Aerobic blood culture of all patients revealed Staphylococcus aureus, which was sensitive to cefotaxime, gentamicin and cloxacillin in case no. 2-4. Case no. 1 was sensitive to only ceftazidime and vancomycin. Doppler flow study results are also summarized in Table I. Platelet count, prothrombin time and KCCT were normal at admission in all patients. Patients were treated with antimicrobial therapy for 6 weeks as per culture and sensitivity and low molecular weight heparin during first 7 days followed by warfarin. The patients were monitored regularly with prothrombin time and KCCT maintaining INR between 2-3 and followed for 6 months for any adverse events. Antithrombin III, Protein C, Protein S and antiphospholipid antibodies measured were within normal limit.

One patient (case no.4) died on day 12 of hospitalization due to pulmonary thromboembolism after 3 days of mechanical ventilation and case no. 1 developed osteomyelitis of right femur that recovered completely with conservative measures. Case no. 2 developed multiple intracranial hemorrhages at 6 weeks, required withdrawal of warfarin therapy and improved with conservative measures. After 6 months, repeat Doppler studies showed absence of thrombus in survivors without any incompetence of ileofemoral valve.

Staphylococcal infection causes a wide spectrum of diseases and carries a mortality of 13-27%(2,3). DVT following staphylococcal septicemia is rare in children and is usually life threatening. The process usually begins in veins of calf around valve cusps or within soleal plexus. It occurs due to release of various exotoxins; alpha-toxins by many strains that act on cell membranes and produce aggregation of platelets and spasm of smooth muscle. In addition, coagulase enzyme released by staphylococci also interacts with fibrinogen and causes plasma to clot and subsequently results in DVT(3). The early color doppler flow study is important for diagnosis of DVT. The criteria for detecting DVT are failure to compress the vascular lumen and absence of normal phasic Doppler flow signals arising from changes to venous flow. The diagnostic sensitivity and specificity of color Doppler study for DVT are approximately 98%(4,5).

Anticoagulation therapy remains the mainstay of initial treatment for DVT. Low molecular weight heparin (LMWH) prevents extension of the thrombus, significantly reduces but does not eliminates the incidence of fatal and nonfatal pulmonary emboli as well as recurrent thrombosis. Heparin therapy has little effect on the risk of developing postphlebitic syndrome. Though thrombolytic therapy (streptokinase, urokinase, rTPA) causes prompt resolution of symptoms, prevention of pulmonary embolism, restoration of normal venous circulation, preservation of venous valvular function, and prevention of postphlebitic syndrome; it does not prevent clot propagation, rethrombosis, or subsequent embolization. Furthermore, heparin therapy and oral anticoagulant therapy must always follow a course of thrombolysis(6). We used antimicrobials, heparin and warfarin in all patients. Thrombolytic agents were not considered because of high cost and non-affordability by parents. Intracranial hemorrhage in one patient could have developed due to interaction of warfarin with macrolide (erythromycin) during follow up therapy.

Surgical therapy for DVT may be indicated when anticoagulation therapy is ineffective or contraindicated. The rationale for thrombectomy is to restore venous patency and valvular function. Thrombectomy alone is not recommended because of high risk of rethrombosis and it should be always followed by heparin therapy.

Deep vein thrombosis should be considered in children with unilateral swollen, tender limb, edema, positive Homan’s sign and local musculoskeletal focus of infection. Early diagnosis by Doppler flow study and treatment with appropriate antibiotics and anticoagulation may be life saving.