Post varicella disseminated intravascular coagulation and transient protein S deficiency in an otherwise healthy 6-year-old boy: a case report

Abstract

Varicella infections are usually considered to be benign, even though varicella disease may cause serious complications. However, in Europe, the incidence of varicella infections (and complications) has been reported to peak in the spring [1]. An increased risk of complications is well known in immunocompromised individuals and in neonates, if maternal varicella has erupted close to birth. Severe complications (0.82/100,000 children/year) can also occur in previously healthy children, including central nervous system manifestations (61%), secondary bacterial infections (38%), haematological disorders (5%) and occasional fatal outcome (6%) [1,2]. Purpura fulminans is a thrombotic disease that can occur during infections, disseminated intravascular coagulation (DIC) or in the context of an acquired or congenital protein C or S deficiency. The importance of protein S and C as two inhibitors in haemostasis is well known because severe inherited deficiency is associated with neonatal purpura fulminans and heterozygous protein S or C deficiency is associated with venous thromboembolism.We report a Caucasian 6-year-old boy with DIC in addition to presumptive vasculitis and endocarditis in the aftermath of a varicella infection.The young patient (height 121 cm, weight 21 kg) was admitted 2 weeks after otherwise uncomplicated chickenpox with painful and bluish discolouration of both lower limbs. The examination revealed normal body temperature and blood pressure. Peripheral pulses were palpable. We found an accelerated heart beat (130/min) and a normal respiratory rate. The skin lesions showed a red to livedolike discolouration, they were significantly painful on palpation and indurated. There was no skin necrosis. On the left lower leg, pretibial superficial skin erosion of 6 cm in diameter was present in addition to an otherwise intact skin. The clinical diagnosis of vasculitis or atypical Henoch-Schönlein purpura was made.Blood investigations showed normal values for the leukocyte count (total leukocytes 11,900/ll, neutrophil granulocytes 67%, lymphocytes 19%), haemoglobin concentration (11.9 g/dl), platelet count (187,000/ll), renal (besides microhaematuria with a maximum of 431 erythrocytes/ll) and liver function tests. There were signs of inflammation (C-reactive protein [CRP] 7.8 mg/dl).Of importance, the coagulation profile was grossly altered: the activated partial thromboplastin time (PTT) was prolonged (52 s, normal \36 s) and the prothrombin time (PT given as the prothrombin ratio [PR]) was reduced (36%). The international normalized ratio (INR) was 2.0. Fibrinogen was significantly reduced (0.4 g/l) and fibrin d-dimers were elevated ([35 mg/l, normal range: 0-0.5 mg/l). There were considerably reduced values of proteins S and C, coagulation factors II, V, VIII and XIII (Fig. 1), whereas coagulation factors VII, IX, X, XI and XII showed normal activities. The serum immunoglobulins G, A and M were normal. The lupus anticoagulant was 37 s (normal range:

Varicella-associated disseminated intravascular coagulation secondary to Henoch-Schönlein purpura with renal and gastrointestinal system involvement in a child: A case report

“…However, there are some critical differences in the clinical manifestations of varicella-associated DIC in immunocompromised patients [6][7][8][9][10][11][12][13][14][15][16][17] and in individuals with protein C and protein S deficiency which causes purpura fulminans. [18][19][20][21][22][23][24][25][26][27] Purpura fulminans is a highly thrombotic subtype of DIC characterized by the overt presentation of erythematous macular skin lesions on the trunk and extremities. [18][19][20][21][22][23][24][25][26][27][28] As previously reported, the immunocompromised patients who developed varicella-associated DIC included recipients of bone marrow, hematopoietic stem cell, or organ transplantation, patients with primary nephropathy who were receiving corticosteroid therapy, cancer patients receiving chemotherapy, and patients with human immune deficiency virus infection.…”

“…[18][19][20][21][22][23][24][25][26][27] Purpura fulminans is a highly thrombotic subtype of DIC characterized by the overt presentation of erythematous macular skin lesions on the trunk and extremities. [18][19][20][21][22][23][24][25][26][27][28] As previously reported, the immunocompromised patients who developed varicella-associated DIC included recipients of bone marrow, hematopoietic stem cell, or organ transplantation, patients with primary nephropathy who were receiving corticosteroid therapy, cancer patients receiving chemotherapy, and patients with human immune deficiency virus infection. [6][7][8][9][10][11][12][13][14][15][16][17] The case reported here is novel because, to our knowledge, there has been no report of VZV-associated DIC developed 24 days after the onset of HSP that has no usual initial clue of varicella.…”

“…However, there are some critical differences in the clinical manifestations of varicella-associated DIC in immunocompromised patients [6–17] and in individuals with protein C and protein S deficiency which causes purpura fulminans. [18–27] Purpura fulminans is a highly thrombotic subtype of DIC characterized by the overt presentation of erythematous macular skin lesions on the trunk and extremities. [18–28]…”

“…[18–27] Purpura fulminans is a highly thrombotic subtype of DIC characterized by the overt presentation of erythematous macular skin lesions on the trunk and extremities. [18–28]…”

Purpura fulminans from reduced protein S following cytomegalovirus and varicella infection

“…PS is an essential cofactor for activated PC, one of the major regulators of hemostasis, which when activated by thrombin/ In children, post infectious PF associated with VZV is welldocumented in the literature. [10][11][12][15][16][17][18][19][20][21][22][23] In these cases, varicella infection has been shown to induce autoantibody formation that results in lowering of both PS total and free antigen. 10,11,20 A variety of mechanisms have implicated infectious agents in the induction of autoimmune diseases, with "molecular mimicry" being the prevailing theory.…”