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Coagulation factor (F) V is a glycoprotein that plays an essential role in the formation of the prothrombinase complex, which is critical for progressing clot formation. FV deficiency is a rare bleeding disorder with an estimated incidence of one per 1 million in the general population. The disorder is manifested with a wide array of clinical bleeding events. The most common bleeding features of FV deficiency are mucosal bleedings. Life-threatening manifestations are rarely seen in this disorder. FV deficiency is diagnosed using routine coagulation tests and FV activity assay. A wide spectrum of mutations including missense, nonsense, and frameshift is observed throughout the F5 gene. Although fresh frozen plasma is the dominant therapeutic choice, a newly introduced plasma-derived FV concentrate was found effective in in vitro correction of prothrombin time, activated partial thromboplastin time, and thrombin generation parameters in severe FV deficiency and should provide more targeted treatment for patients with FV deficiency in the future.

Comprehensive proteomic analyses of human and murine platelets established an extraordinary intracellular repertoire of signaling components, which control crucial functions. The spectrum of platelet serine/threonine protein kinases (more than 100) includes the AGC family (protein kinase A, G, C [PKA, PKG, PKC]), the mitogen-activated protein kinases (MAPKs), and others. PKA and PKG have multiple significantly overlapping substrates in human platelets, which possibly affect functions with clear “signaling nodes” of regulation by multiple protein kinases/phosphatases. Signaling nodes are intracellular Ca2+ stores, the contractile system (myosin light chains), and other signaling components such as G-proteins, protein kinases, and protein phosphatases. An example for this fine-tuning is the tyrosine kinase Syk, a crucial component of platelet activation, which is controlled by several serine/threonine and tyrosine protein kinases as well as phosphatases. Other protein kinases including PKA/PKG modulate protein phosphatase 2A, which may be a master regulator of MAPK signaling in human platelets. Protein kinases and in particular MAPKs are targeted by an increasing number of clinically used inhibitors. However, the precise regulation and fine-tuning of these protein kinases and their effects on other signaling components in platelets are only superficially understood—just the beginning. However, promising future approaches are in sight.

Patients who suffer from inherited or acquired thrombocytopenia can be also affected by platelet function defects, which potentially increase the risk of severe and life-threatening bleeding complications. A plethora of tests and assays for platelet phenotyping and function analysis are available, which are, in part, feasible in clinical practice due to adequate point-of-care qualities. However, most of them are time-consuming, require experienced and skilled personnel for platelet handling and processing, and are therefore well-established only in specialized laboratories. This review summarizes major indications, methods/assays for platelet phenotyping, and in vitro function testing in blood samples with reduced platelet count in relation to their clinical practicability. In addition, the diagnostic significance, difficulties, and challenges of selected tests to evaluate the hemostatic capacity and specific defects of platelets with reduced number are addressed.

BACKGROUND Immediate reporting of critical values or test results significantly outside the normal range has a growing role in the management of patients, especially in life-threatening conditions. Due to the lack of international consensus, diverse approaches are used for determination of thresholds, reporting, documentation, and follow-up. In this study, we assessed how Iranian laboratories manage critical values for hemostasis. METHODS We designed a standard questionnaire to assess different aspects of hemostasis critical values, including the number of coagulation tests with a defined critical value, critical values reporting, documentation, and follow-up policies. All results were self-reported and correctness of the data was not assessed by the authors. RESULTS A total of 166 (66.4%) out of 250 laboratories completed the questionnaire; most (52.4%) were private. About 97% of responding laboratories had a critical values policy. These were defined for 64.3% (n: 27) of all coagulation tests (n: 42) performed in Iranian laboratories. Activated partial thromboplastin time (APTT), prothrombin time/international normalized ratio (PT/INR), platelet count, factor XI, and factor XIII assays had defined critical values among all laboratories performing these tests. Almost all laboratories reported critical values within 1 hour, after confirmation of the result on the same sample (70% of the laboratories) or a new one (13.4% of the laboratories). State and private laboratories had the same critical value reporting policy for in and outpatients, with laboratory technicians reporting critical results to nurses, for the most part. CONCLUSION Although critical value policy is widely used among Iranian laboratories, there is no consensus policy for the reporting of hemostasis critical values, or documentation, threshold determination, and follow-up processes. It is impossible to determine whether non-responding laboratories had any critical values reporting policy. Results thus are biased toward laboratories that did.

von Willebrand disease (VWD) is the most common congenital bleeding disorder with an estimated incidence of 1% in the general population. The disorder is classified into three main types: type 1 and type 3 as quantitative deficiency and type 2 as qualitative defects. The bleeding tendency is highly variable in VWD, ranging from an asymptomatic condition, mainly in type 1 VWD, to severe life-threatening hemorrhage, most notably in type 3 VWD. Diagnosis of the disorder is sophisticated and requires advanced laboratory testing and precise clinical assessment. Bleeding symptoms, decreased VWF level and/or activity, and the pattern of inheritance are three main criteria for appropriate and timely diagnosis of VWD. Although on-demand therapy is the mainstay of treatment in VWD, long-term prophylaxis is recommended for those with recurrent and severe hemorrhages. Different therapeutic choices are available in VWD including VWF/FVIII concentrates, recombinant VWF, desmopressin, and, in some locations, fresh frozen plasma (FFP). With timely diagnosis and appropriate management of the VWD, the burden of the disorder can be alleviated or even eliminated.