Screening tests for defects in primary Hemostasis :
In addition to the coagulation-factor tests described above, it often is important to screen for abnormalities in primary hemostasis such as vWD or platelet-function abnormalities. The traditional test used has been the template bleeding time and often is included as part of initial screening for a bleeding disorder. Questions regarding the reliability, sensitivity, specificity, and predictability of the bleeding time, however, have led to a decline in its use. Platelet aggregation studies are extremely useful in identifying an abnormality in platelet function. It should be noted that normal numbers of platelets are needed for primary hemostasis and no functional tests should be done in patients with thrombocytopenia.

Platelet Aggregation studies :
Platelet aggregation studies measure the degree and pattern of platelet aggregation after the addition of platelet agonists (adenosine diphosphate, epinephrine, collagen, thrombin, arachidonate, ristocetin). The patterns of aggregation observed can aid in the detection and definition of platelet function disorders such as storage pool defects, Bernard-Soulier syndrome, or Glanzmann's thrombasthenia. Platelet aggregation testing and interpretation is typically performed only in specialized laboratories. Flow cytometry is a newer tool, which can be used to directly detect platelet membrane glycoproteins.

Clinical scenarios encountered in patients being evaluated for bleeding disorders The presentation of the bleeding patient can be quite variable and all instances are not addressed in this article. The common hemorrhagic problems associated with leukemia and aplastic anemia are not discussed here, except to mention that bruising and petechiae frequently are present at diagnosis and are often the reason the child is first brought to medical attention. The presence of anemia, leukocyte abnormalities, adenopathy, and/or hepatosplenomegaly, however, signifies distinct differences from other bleeding disorders and immediately changes the focus of inquiry.

• Significant bleeding history, normal PT, normal aPTT, and normal Platelet count :
  The important consideration here is the clinician's impression that the bleeding history is significant. That being the case, despite the normal screening test results, further work-up is warranted. This scenario could be due to vWD, factor XIII deficiency, defects in fibrinolysis, or platelet function disorders.
  
  
• History of bleeding and isolated prolongation of the aPTT :
  An isolated prolongation of the aPTT can be due to an inhibitor, heparin contamination, or deficiency in the intrinsic pathway of coagulation, excluding those factors in the common pathway (factors V, X, prothrombin, and fibrinogen). Of the remaining factors (high molecular weight kininogen, factors VIII, IX, XI, and XII), only deficiencies of three (VIII, IX, and XI) result in a bleeding diathesis. As discussed previously, vWD can present with this scenario, depending on the magnitude of factor VIII deficiency. Bleeding history with an isolated PT prolongation Factor VII is the only factor tested for by the PT that is not part of the common pathway. In the absence of an inhibitor, isolated prolongation of the PT is consistent with factor VII deficiency; however, factor VII deficiency is a rare entity and there are other possibilities that the clinician should consider. Because factor VII has the shortest half-life of all clotting factors, plasma levels drop most rapidly in situations affecting the production of multiple procoagulants (e.g., warfarin ingestion or acute liver failure). Thus, prolongation of the PT would be expected acutely, prior to prolongation of the aPTT. Similarly, in most laboratories, the PT is more sensitive to deficiencies of the vitamin K-dependent factors (factors II, VII, IX and X) than is the aPTT.
  
  
• History of bleeding and prolongation of both PT and aPTT with a normal platelet count Prolongation of both the PT and aPTT in a symptomatic patient can be indicative of deficiency of one or more common pathway factors. Deficiency of a single factor in the common pathway (factor V, X, prothrombin) can prolong both of the coagulation times: however, such conditions are rare. Deficiency of multiple factors from both the intrinsic and extrinsic pathways may have a single etiology and also prolong both the PT and aPTT.
  
  
• History of bleeding and prolongation of PT and aPTT and thrombocytopenia :
  This is most commonly encountered in sick children, with the bleeding and hematologic abnormalities reflecting DIC or liver failure. A careful history and physical examination typically provides the diagnosis. Although the diagnosis is mainly clinical, laboratory testing can be used to support the diagnosis of DIC. Typical laboratory abnormalities include decreased fibrinogen concentration, decreased factor V and VIII activity, and reduced levels of antithrombin III. Fibrin degradation products and D-dimers, which are specific for the degradation of fibrin, usually are elevated.
  
  Liver is the primary site of synthesis for the majority of procoagulant and fibrinolytic proteins and protease inhibitors. Liver dysfunction due to any number of diseases results in an imbalance in the hemostatic system, often resulting in predisposition toward bleeding in response to trauma or surgical procedures. As in DIC, both the PT and aPTT are typically prolonged due to deficiencies in multiple factors. In contrast to DIC, factor VIII levels are typically normal or elevated. Thrombocytopenia may also be present due to portal hypertension and associated splenic sequestration.
  
  
• A child with petechiae and/or mucosal bleeding associated with isolated thrombocytopenia :
  ITP in children most commonly is acute, but 10-15% of children have chronic ITP. Acute ITP is a self-limited acquired bleeding disorder due to the production of autoantibodies targeted against the patient's platelets. The typical presentation is an otherwise healthy child, with an acute onset of bleeding symptoms; most often diffuse petechiae and bruising. Less commonly, epistaxis, oral bleeding, hematuria, and gastrointestinal bleeding may be seen. Besides thrombocytopenia, there are no other hematologic abnormalities, although mild anemia may be present if there has been significant hemorrhage. Review of the smear sometimes reveals typical lymphocytes due to recent viral illnesses, but there are no other leukocyte abnormalities. Both large and normal sized platelets are seen.
  
  
• Asymptomatic child with a prolonged aPTT or PT :
  This scenario is usually encountered when a child has screening coagulation studies obtained prior to a surgical procedure such as a tonsillectomy. Although the utility of such screening is debatable, the abnormal studies must be explained. The causes of prolonged PT and aPTT associated with bleeding have already been discussed; however, in the child without previous bleeding history and a negative family history, the approach to diagnosis may take a different path. The most common cause of such abnormal results is a circulating inhibitor, ultimately not associated with bleeding. Other causes of abnormal coagulation screening tests without a true bleeding disorder include deficiency of the contact factors prekallikrein, high molecular weight kininogen, or factor XII. Deficiencies of these factors may prolong the aPTT, but do not cause bleeding. On the contrary, factor XII deficiency is thought to represent a mild risk factor for thrombosis.