Scrotal Swelling: An Unusual Presentation of Protein C Deficiency
The protein C pathway provides important contributions to maintain the ﬂuidity of the circulation, prevent thrombosis, and protect the integrity of the vasculature in response to injury. This article presents a 28-day-old male with a scrotal swelling and protein C deﬁciency. The infant improved with disappearance of the scrotal swelling and he was discharged on warfarin to prevent further thrombosis. A scrotal swelling could be the ﬁrst manifestation of thrombosis resulting from protein C deﬁciency.
Protein C is a vitamin K-dependent coagulation protein, which plays an essential role in the regulation of thrombin. It is synthesized within the hepatocytes and circulates in plasma in a very low concentration. Activated Protein C, supported by protein cofactors (Protein C and factor V) and lipid cofactors, cleave speciﬁc sites in the activated procoagulant factors Va and VIIIa (Figure 1) when they have been activated by the small amounts of thrombin produced in the initiation phase of coagulation activation.[1,2] Clinically, patients with protein C and S deﬁciency are at an increased risk of venous thromboembolic disease, occasional arterial thrombosis, neonatal purpura fulminans, portal vein thrombosis, and even childhood strokes.[3,4]
A 28-day-old infant born out of non-consanguineous marriage having good weight gain presented with excessive crying and swelling and redness of the left scrotum. Scrotal ultrasound revealed normal testes and epididymis with normal color ﬂow, and a hydrocoele with internal echoes on the left side and hydrocoele without internal echoes on the right side. Septic screen was negative, liver functions and renal functions were normal.
The next day, baby developed abdominal distension with ascites. Abdominal ultrasound did not show hepatomegaly. A diagnostic ascitic tap (paracentesis) showed normal results and sterile culture, thus sepsis was ruled out. After 7 days, in view of persistent abdominal distension, a repeat ultrasound was done that showed evidence of thrombosis of portal vein and umbilical vein with portal hypertension. Low molecular weight heparin and propranolol were added.
A repeat ultrasound was done when the infant was 40 days old which showed evidence of portal vein thrombosis at the porta and its branches with minimal color ﬂow (partial recannalisation) without collaterals and ascites with splenomegaly. Thrombosis of right external iliac and right common femoral vein with ascites was noted, however hepatic arteries, inferior vena cava, and hepatic veins were normal. Baby was discharged on warfarin and had good weight gain with no new evidence of thrombosis. The hydrocoele resolved at follow up.
Investigations done showed total leukocyte counts of 19,500/µL with hemoglobin of 10.7g/dL and platelet count of 3,10,000/mL, blood culture and cerebrospinal ﬂuid culture showed no growth. Renal function tests were normal. Blood urea of 24 mg/dL and serum creatinine of 0.5 mg/dL with normal electrolytes. Serum bilirubin 1.4 mg/dL, serum glutamic-oxaloacetic transaminase (SGOT) 46 IU, serum glutamic-pyruvic transaminase (SGPT) 48 IU, alkaline phosphatase (ALP) of 142 U/L and albumin 1.9 g/dL. Urine routine was normal and culture was sterile. Prothrombin time was 20 seconds with INR of 1.5 and Protein C activity of 28%.
The exact incidence of protein C and protein S deﬁciency in our population is not known. Protein C deﬁciency is one of the causes of curable or preventable portal vein thrombosis. Acquired causes of protein C and S deﬁciencies are seen in acquired illness like liver disease, disseminated intravascular coagulation (DIC), therapy with L-asparaginase and coumarin, and acute severe bacterial infections.[1,5]
The sepsis workup was negative thus ruling out sepsis as a cause of the thrombotic state. The progression of abdominal distension with ascites and portal vein thrombosis without prior history of umbilical catheterization suggests a hypercoagulable state. The possibility of protein C, protein S and antithrombin III deﬁciency was considered. However, only protein C levels were done due to ﬁnancial constraints, and the patient responded well to anticoagulation measures and propranolol.
The physiologic importance of the protein C system is best illustrated by the manifestation of massive thrombotic complications in infants with protein C deﬁciency. Neonatal purpura fulminans, a rapidly progressing hemorrhagic necrosis of the skin due to microvascular thrombosis, inﬂammation, and disseminated intravascular coagulation (DIC), is typically observed in severe protein C deﬁciency, whereas heterozygous protein C deﬁciency in adults carries a signiﬁcantly increased risk for venous thrombosis.
The scrotal swelling in this case, subsided with conservative management. Protein concentrate replacements exist for protein C and antithrombin and these can be considered for the treatment of newborn infants with thrombosis and less than 30% antithrombin or 20% protein C in the term infant, and less than 15% antithrombin or 10% protein C in the preterm. Acquired protein C deﬁciency is also found in patients with severe infection and sepsis, most likely due to consumption and poor synthesis in the liver, and low protein C levels correlate with poor clinical outcome and death.
Scrotal swelling may be the ﬁrst presentation of mild protein C deﬁciency and screening for it at presentation would help in preventing further thrombosis.
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