The fate of a Military Pilot in Malaysia: Lingering on the ground after young stroke

Strokes in young pilots can result in the devastating loss of productive years of life, especially for pilots at the peak of their careers. A 32-yr-old male military helicopter pilot was diagnosed with superior sagittal sinus thrombosis and bilateral parietal hemorrhages secondary to protein S deficiency after 15 years in military service. Two years post-stroke, he was carefully evaluated for a possible return to work after aeromedical assessment and the 1 percent rule being considered. A decision was made by the medical board for him to be disqualified to fly and grounded with work accommodation. The authors recommend that there is a need for reassessment up to two years using the objective PULHEEMS method for young pilots who failed aeromedical assessment due to stroke for returning to work as their experiences and knowledge is highly valuable.

Chylopericardium due to Subclavian Vein Thrombosis in the Setting of Protein S Deficiency

Background. Chylopericardium is the accumulation of lymphatic fluid in the pericardial cavity. It can be idiopathic or secondary to trauma, cardiothoracic surgery, neoplasm, radiation, tuberculosis, lymphatic duct dysfunction, thrombosis, or other causes. We present a case of chylopericardium due to subclavian vein thrombosis in a patient with protein S deficiency. Clinical Case. A 48-year-old man with a history of protein S deficiency presented to the emergency department with shortness of breath and a productive cough. CT of the chest showed pulmonary emboli, moderate pericardial effusion, and a large thrombus of the superior vena cava, brachiocephalic vein, and subclavian veins. He developed echocardiographic evidence of cardiac tamponade so he underwent pericardiocentesis with drainage of milky-appearing fluid. Analysis of the fluid showed elevated triglycerides consistent with chylopericardium. The pericardial effusion reaccumulated, likely secondary to lymphatic duct obstruction due to his subclavian vein thrombus. Catheter-assisted thrombolysis was performed with resolution of the patient’s effusion and symptoms. Conclusion. Chylopericardium is a rare but important complication of subclavian vein thrombosis. Management is typically with surgical intervention, although our case represents successful treatment with catheter-assisted thrombolysis.

Intracranial Major Artery and Venous Sinus Thrombosis in a Young Male with MTHFR Mutation and Protein S Deficiency

This case represents a unique example of stroke in a young patient involving major venous sinuses as well as major artery in a span of 6 months. After evaluation, he was found to have an abnormal thrombophilia profile. In young patients with recurrent stroke, investigating for an abnormal thrombophilia profile is crucial.

Resolution of possible acquired protein S deficiency after viral suppression in HIV infection

Current literature suggests an increased risk of venous thromboembolism (VTE) in people living with HIV (PLWH) with poorly controlled viraemia and immunodeficiency. VTE treatment guidelines do not specifically address anticoagulation management in PLWH. We report a case of a 33-year-old woman diagnosed with an unprovoked pulmonary embolism (PE) and deemed protein S deficient. Three years later, she was diagnosed with AIDS. Antiretroviral therapy (ART) was promptly initiated with viral suppression and immune reconstitution within 12 months. Eight years after her initial PE, the patient self-discontinued warfarin. Multiple repeat protein S values were normal. ART without anticoagulation has continued for 3 years with no thrombotic events. This case describes a patient with VTE presumably secondary to undiagnosed HIV with possible consequent acquired protein S deficiency. Additional research is needed to understand the characteristics of PLWH with VTE who may warrant long-term anticoagulation as opposed to shorter courses.

First report of inherited protein S deficiency caused by paternal PROS1 mosaicism

Not available.

Genetic Variants in the Protein S (PROS1) Gene and Protein S Deficiency in a Danish Population

Protein S (PS) deficiency is a risk factor for venous thromboembolism (VTE) and can be caused by variants of the gene encoding PS (PROS1). This study aimed to evaluate the clinical value of molecular analysis of the PROS1 gene in PS-deficient participants. We performed Sanger sequencing of the coding region of the PROS1 gene and multiplex ligation-dependent probe amplification to exclude large structural rearrangements. Free PS was measured by a particle-enhanced immunoassay, while PS activity was assessed by a clotting method.A total of 87 PS-deficient participants and family members were included. In 22 index participants, we identified 13 PROS1 coding variants. Five variants were novel. In 21 index participants, no coding sequence variants or structural rearrangements were identified. The free PS level was lower in index participants carrying a PROS1 variant compared with index participants with no variant (0.51 [0.32–0.61] vs. 0.62 [0.57–0.73] × 103 IU/L; p < 0.05). The p.(Thr78Met) variant was associated with only slightly decreased free PS levels (0.59 [0.53–0.66] × 103 IU/L) compared with the p.(Glu390Lys) variant (0.27 [0.24–0.37] × 103 IU/L, p < 0.01). The frequency of VTE in participants with a coding PROS1 variant was 43 and 17% in the group with normal PROS1 gene (p = 0.05).In conclusion, we report 13 PROS1 coding variants including five novel variants. PS levels differ by PROS1 variant and the frequency of VTE was higher when a coding PROS1 variant was present. Hence, molecular analysis of the PROS1 gene may add clinical value in the diagnostic work-up of PS deficiency.

Midbrain infarction in inherited protein S deficiency: a rare association

Inherited thrombophilic disorders are well‐established predisposing factors for venous thromboembolism, but their role in arterial ischaemic stroke is uncertain. The exact mechanism of arterial thrombosis in thrombophilias remains elusive. Herein, we report a case of a 30-year-old woman who was admitted to our facility with sudden-onset right-sided ptosis and ophthalmoplegia. Detailed clinical features, neuroimaging and laboratory evaluation clinched the diagnosis of ischaemic stroke in midbrain due to microvascular obstruction associated with isolated protein S deficiency. She was treated with oral anticoagulant (warfarin) and physiotherapy; without any improvement of her symptoms at 2 months of follow-up. A high index of clinical suspicion is needed in any case of young ischaemic stroke in absence of common cardiac and vascular risk factors, to recognise the presence of inherited thrombophilia.