A 16-year-old boy is evaluated for excessive skin bruising occurring over the last 6 weeks. There is no personal or family history of excessive bleeding. The patient has a history of chronic kidney disease and is waiting for a renal transplant. Laboratory studies are as follows:
| Hemoglobin | 9.5 g/dL |
| Platelets | 200,000/mm3 |
| Blood urea nitrogen | 50 mg/dL |
| Creatinine | 4.4 mg/dL |
| PT | 12 sec |
| Activated PTT | 23 sec |
Which of the following is the most likely cause of this patient's bruising?
Show Explanatory Sources
This patient has chronic kidney disease (CKD) with excessive bruising, a normal platelet count, and normal coagulation studies. These findings are suggestive of platelet dysfunction, a common cause of easy bruising and mucosal bleeding in patients with CKD.
Normally, primary hemostasis consists of the formation of a platelet plug. This process begins with binding of von Willebrand factor (vWF) to the denuded endothelium after injury; vWF creates a bridge between subendothelial collagen and platelets (adhesion). Platelets are then activated and release substances (eg, ADP, thromboxane A2) to promote aggregation (ie, platelet-to-platelet clumping via binding of fibrinogen to the glycoprotein IIb/IIIa receptor).
In CKD, platelet function is thought to be disrupted due to inappropriate upregulation of nitric oxide. Patients with CKD have elevated urea, the end product of ammonia breakdown, which is derived from arginine. As urea levels rise, arginine and its precursors are shunted to a different pathway, instead producing guanidinosuccinic acid (GSA), a precursor to nitric oxide. Inappropriately high nitric oxide levels in CKD inhibit primary hemostasis via the following mechanisms:
Decreased platelet adhesion: Nitric oxide downregulates vWF secretion by endothelial cells.
Decreased activation and aggregation: Nitric oxide leads to reduced levels of ADP and thromboxane A2. In addition, it inhibits activation of the glycoprotein IIb/IIIa receptor.
Anemia in CKD (due to reduced erythropoietin production) can also contribute to platelet dysfunction by reducing platelet marginalization along the endothelial surface.
(Choice A) Bruising due to atrophy of dermal collagen describes senile purpura (ie, benign purple patches on the hands/forearms in patients age ≥65); this patient's age is inconsistent with this diagnosis.
(Choice B) Bleeding complications are typical of acute disseminated intravascular coagulation (DIC), a consumptive coagulopathy. However, most patients have an acute risk factor (eg, sepsis, trauma), and PT and PTT would be prolonged. Coagulation studies in chronic DIC may be normal, but these patients typically have thrombosis and a history of malignancy.
(Choice D) Easy bruising is a common finding in factor VIII deficiency (hemophilia A), but PTT would be prolonged. In addition, symptoms usually develop by age 2.
(Choice E) Vitamin K deficiency can cause easy bruising, but PT would be prolonged.
Educational objective:
Chronic kidney disease increases the risk for platelet dysfunction, which is thought to be due to inappropriately upregulated nitric oxide, causing decreased platelet adhesion, activation, and aggregation. Coagulation studies and platelet count are typically normal.