Platelet function defects (PFD) should be considered in patients with symptoms suggestive of a defect in primary hemostasis. A genetic disorder may be present, particularly if symptoms are lifelong or familial; however, most PFD encountered in clinical practice are acquired. An acquired PFD may be the cause of excessive bleeding, but it may also be an incidental finding or a purely in vitro phenomenon. The complex laboratory…

The platelet is a dynamic structure, covered externally with glycoprotein (GP) receptors. Internally, the platelet possesses alpha (α) granules, which contain a number of proteins, including von Willebrand factor (VWF), fibronectin, and fibrinogen; and dense (δ) granules, containing adenosine triphosphate (ATP), adenosine diphosphate (ADP), serotonin, pyrophosphate, magnesium, and calcium. Primary hemostasis is initiated by platelet adhesion to vessel wall components at the site of vessel injury.…

The platelet function analyzer (PFA)-100 is the most widely used global test of primary hemostasis. It performs an in vitro test of platelet plug formation, referred to as the PFA, by measuring the time to occlusion of a window in a coated membrane through which blood is forced at high shear rate. It was designed to replace the bleeding time (BT) test, which is no longer recommended.…

von Willebrand disease (VWD) may be treated by 1) raising the patient’s own von Willebrand factor (VWF), 2) replacement of VWF, or 3) use of adjuvant therapies with a global effect on hemostasis. A treatment plan must be based on an accurate diagnosis of the type and severity of VWD present in the patient, as described in Chapter 134 , and the specific clinical situation (e.g.,…

Acquired von Willebrand syndrome (AVWS) is a rare disorder in which laboratory findings and clinical symptoms mimic various types of von Willebrand disease (VWD). It may be suspected in a patient with abnormal VWD tests and no previous history of excessive bleeding, who has one of the disorders and conditions listed in Table 135.1 or one with a similar mechanism. The International Registry on AVWS (…

von Willebrand factor (VWF) is a large adhesive glycoprotein required for platelet adhesion to subendothelium at the site of vessel injury, platelet–platelet interaction to form the platelet plug, and stabilization of factor VIII (FVIII) in the circulation. Deficiency or defect of VWF leads to the common disorder of hemostasis, von Willebrand disease (VWD). Many cases of VWD, but not all, are due to defects in the…

Coagulation factor inhibitor assays are used to identify inhibitors occurring in individuals with inherited factor deficiencies (alloantibodies) and those not congenitally deficient (autoantibodies). Alloantibodies are sought when congenitally deficient patients fail to respond to appropriate therapy. Autoantibodies are suspected when low factor levels occur in previously unaffected patients, particularly when multiple dilutions of patient plasma give different factor activity levels, suggesting that the patient’s dilution curve…

Coagulation factors may be measured by methods assessing both their presence, as antigens, and their ability to function, as activity. Inherited coagulation factor deficiencies may be of two types. Type I defects (quantitative) have decreased absolute amounts of the factor, resulting in both decreased activity and antigen levels. They result from lack of production or increased clearance of the gene product. Type II defects (qualitative) have…

In mixing studies, patient plasma with a prolonged activated partial thromboplastin time (PTT) or prothrombin time (PT) is mixed with normal pool plasma (NPP). PTT or PT is measured after mixing the two samples. Mixing studies are used to distinguish among potential causes for prolonged screening test results—in particular, to distinguish between a factor deficiency and the presence of an inhibitor. Methods The standard procedure for…