From the Guidelines
Protein C deficiency can lead to severe complications of disseminated intravascular coagulation (DIC), including organ damage, severe hemorrhage, and potentially death, emphasizing the need for prompt treatment and management. The complications of DIC in protein C deficient patients are multifaceted, involving widespread clotting throughout small blood vessels, depletion of clotting factors, and a heightened risk of severe bleeding due to the lack of protein C's natural anticoagulant properties. Key complications include:
- Organ damage from microvascular thrombosis
- Severe hemorrhage
- Purpura fulminans, a life-threatening condition causing skin necrosis
- Potentially death if not treated promptly
Management of cancer-associated DIC, as guided by the International Society on Thrombosis and Haemostasis (ISTH) 1, emphasizes the importance of treating the underlying cause, which in the context of protein C deficiency, involves addressing the deficiency itself. While the ISTH guidance focuses on cancer-related DIC, the principles of managing DIC can be applied broadly, including in cases of protein C deficiency. The recommendation for prophylactic anticoagulation in patients with DIC, except in cases of hyperfibrinolytic DIC, highlights the delicate balance between preventing thrombosis and avoiding exacerbation of bleeding. In protein C deficiency, the use of protein C concentrate, fresh frozen plasma, and heparin therapy, as appropriate, can be crucial in managing DIC complications. Close monitoring of coagulation parameters, including platelet count, fibrinogen, D-dimer, and prothrombin time, is essential for guiding treatment and preventing further complications, as emphasized by the need for regular clinical and laboratory surveillance 1.
From the Research
Complications of Protein C Deficiency and DIC
- Disseminated intravascular coagulation (DIC) is a reflection of an underlying systemic disorder that affects the coagulation system, resulting in pro-coagulant activation, fibrinolytic activation, and consumption coagulopathy, which may lead to organ dysfunction and death 2.
- Protein C deficiency can lead to purpura fulminans, venous thrombosis, and/or pulmonary embolism in symptomatic heterozygous patients, while homozygous patients may develop severe and often fatal purpura fulminans and DIC during the neonatal period 3.
- Homozygous protein C deficiency can be treated with fresh frozen plasma, intravenous protein C concentrate, or coumarin derivatives, while heterozygous patients can be treated with oral anticoagulation or heparin therapy 3, 4.
Treatment of DIC in Protein C Deficiency
- Activated protein C (APC) has been shown to improve DIC more efficiently than heparin without increasing bleeding, and may be a better alternative 5.
- Low molecular weight heparin (LMWH) is an effective form of long-term therapy for homozygous protein C deficient patients with measurable protein C levels, and can suppress biochemical markers of in vivo thrombin generation 4.
- Treatment with APC reduced 28-day mortality in patients with severe sepsis, including those with sepsis-associated DIC, but increased the bleeding risk, leading to its withdrawal from the market 6.
Management of Protein C Deficiency and DIC
- Early diagnosis and prompt treatment of DIC, backed by laboratory support, can reduce morbidity and mortality associated with it 2.
- Maintenance of a symptom-free life in protein C deficient patients depends on response to therapy, and patients responding well to treatment can expect normalization of haemostasis and improvement of microcirculation 3.
- The efficacy and safety of other anticoagulants, such as unfractionated heparin or transfusion of platelet concentrates or clotting factor concentrates, have not been objectively assessed in the treatment of DIC 6.