Hermansky-pudlak syndrome and prolonged activated partial thromboplastin time

Abstract

Abstract A patient with a history of oculocutaneous albinism and easy bruising and a family history of the same presented to our health care center. Complete blood count and peripheral smear were normal. Platelet aggregation studies showed storage pool deficiency fulfilling the diagnostic criteria for Hermansky-Pudlak syndrome (HPS). Incidentally, the activated partial thromboplastin time (aPTT) was slightly prolonged at 35.7 s (normal, 24.6 – 34.7 s). Mixing studies and factor levels were not performed due to the mild nature of the aPTT prolongation. Protime (PT) and von Willebrand factor panel were normal. Literature review of all 890 articles on HPS in the PubMed database disclosed occasional case reports of prolonged aPTT, which usually was slight and usually was associated with mild bleeding symptoms and normal PTs. Of interest, Harrison (Arch Dis Child 2002) reported “an unexplained prolongation of the activated partial thromboplastin time in one kindred.” Yousaf (Pigment Cell Melanoma Res 2016) reported a prolonged aPTT in eight of 12 patients tested from six Pakistani families. Hurford (Int J Clin Exp Pathol 2008) performed further testing on a patient with an aPTT of 38.7s (normal, 25.2 – 36.0s): “The APPT mixing study corrected immediately at 34 seconds but prolonged to 36.7 seconds at 2 hours. The coagulation factors VIII, IX, XI and XII, vWF antigen and ristocetin cofactor were all normal. Serum anticardiolipin levels were increased for IgA (17.8 APL; normal < 13). IgG and IgM levels were normal. The TTI and DVVRT test were normal.” A potential mechanism for aPTT prolongation in HPS is locally reduced calcium iron concentration due to absence of platelet dense granules, which store calcium. Calcium facilitates the activation of factors IX, X, and II. Locally reduced calcium ion concentration could impede these reactions and thus prolong the aPTT. In conclusion, mild aPTT prolongation occurs in HPS infrequently and appears to cluster in kindreds. Locally reduced calcium ion concentration due to absence of dense granules is a potential mechanism. Future research should explore this mechanism and other potential mechanisms for aPTT prolongation in HPS.