Is a low level of protein C activity during a pulmonary embolism (PE) concerning for protein C deficiency?

From the Guidelines

A low level of protein C activity during a pulmonary embolism (PE) is not a reliable indicator of protein C deficiency. During acute thrombotic events like PE, protein C levels can be temporarily decreased due to consumption in the clotting process, making test results misleading [ 1 ]. Additionally, anticoagulant medications can artificially lower protein C levels. For accurate diagnosis of protein C deficiency, testing should be performed at least 2-3 weeks after completing anticoagulation therapy and resolution of the acute thrombotic event. Some key points to consider in the management of PE include:

• Initiation of anticoagulation without delay in patients with high or intermediate clinical probability of PE [ 1 ]
• Use of low molecular weight heparin (LMWH) or fondaparinux over unfractionated heparin (UFH) for most patients [ 1 ]
• Preference for non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) when oral anticoagulation is started [ 1 ] Ideally, protein C activity should be measured twice, 4-6 weeks apart, with levels consistently below 70% suggesting hereditary deficiency. If protein C deficiency is suspected as the cause of PE, genetic testing may be warranted, especially with a family history of thrombosis. Proper timing of testing is essential to avoid misdiagnosis and inappropriate management of patients with thrombotic disorders.

From the Research

Protein C Deficiency and Pulmonary Embolism

• A low level of protein C activity during a pulmonary embolism (PE) can be concerning for protein C deficiency, as protein C plays a crucial role in anticoagulation and preventing vascular thrombosis disease 2.
• Hereditary protein C deficiency is a risk factor for pulmonary embolism in adults, and pathogenic variants of the PROC gene have been identified as a cause of protein C deficiency 2.
• Patients with protein C deficiency may present with purpura fulminans, venous thrombosis, and/or pulmonary embolism, and therapeutic options include oral anticoagulation, heparin therapy, and fresh frozen plasma (FFP) 3.

Diagnosis and Treatment

• Diagnosis of protein C deficiency can be made by measuring plasma protein C concentrations or activity, and congenital thrombophilia should be considered in young patients with recurrent lower deep venous thrombosis and pulmonary embolism without obvious predisposing causes 4.
• Treatment of protein C deficiency typically involves anticoagulation therapy, and vitamin B6 and B12 may be added to improve symptoms 4.
• In patients with acute pulmonary embolism, therapeutic anticoagulation remains the mainstay of therapy, and thrombolysis may be considered in massive or submassive PE 5.

Clinical Management

• Clinical management of protein C deficiency involves long-term management of severe heterozygous and homozygous deficiencies, and various therapeutic options are available, including oral anticoagulation, heparin therapy, and liver transplantation 3.
• Maintenance of a symptom-free life depends on response to therapy, and patients responding well to treatment can expect normalization of haemostasis and improvement of microcirculation 3.
• The optimal treatment duration for patients with protein C deficiency and pulmonary embolism will vary depending on the type of initial event, age, and time passed since the initial thromboembolic episode 6.