Approach to the Pediatric Patient With a Bleeding Disorder

Am I Dealing With Bleeding Disorder?

This question helps characterize clinically significant bleeding. History should include the most common site, type and duration of bleeding, medication and herbal history, and bleeding on exposure to hemostatic challenge (procedures such as tonsillectomy, wisdom teeth extraction, circumcision, menstrual history, postpartum bleeding if appropriate). Family history of bleeding should be obtained along the same lines. Objective characterization of the bleeding phenotype can be done using standardized bleeding questionnaires to quantitate bleeding symptoms. Pediatric Bleeding Questionnaire (PBQ) provides a comprehensive assessment of bleeding symptoms. PBQ has high negative predictive value (99%) and low positive predictive value (14%) for von Willebrand disease (VWD). Thus, PBQ is a valuable tool to rule out VWD. Physical exam should include the pattern of bruising and assessment for joint hypermobility. The Beighton scoring system is easy method to assess joint hypermobility. It is worth noting that bleeding disorders can be silent in children who have not yet faced a hemostatic challenge and family history, specifically pattern of inheritance (X-linked recessive vs. autosomal dominant disorders), plays a key role in these cases. The common bleeding symptoms are elaborated below:

• Bruising: The first step in evaluation of bruises in children is to rule out nonaccidental trauma. Inflicted trauma is most likely to manifest over the head, chest, back, and the long bones and may retain the outlines of the instrument. Bruises associated with primary defects of hemostasis are usually located over areas of typical childhood trauma, such as the bony protuberances of extremities or spinous processes. Bruises that are not limited to distal extremities, are larger than a quarter coin, and are associated with hematomas and bruising out of proportion to the mechanism of injury are likely suggestive of underlying bleeding disorder. Intramuscular hematomas usually present with large bruises along with swelling and pain with use of the affected muscle.

• Epistaxis: Epistaxis is usually due to local factors such as trauma, allergic rhinitis, or dry nasal mucosa but is also a common presenting symptom of an underlying bleeding disorder. Bleeding disorders are diagnosed in 25%–33% of patients referred to pediatric hematology for recurrent epistaxis. The clinical significance of epistaxis is enhanced by requiring emergency department visit, occurring in both nostrils, and occurring in association with other bleeding signs and a family history of similar bleeding. Hereditary hemorrhagic telangiectasia may manifest as mucosal bleeding especially epistaxis.

• Hemarthrosis: Joint effusion, warmth, and pain are indicative of acute joint bleed while limited range of motion, synovial thickening, and chronic pain are indicative of chronic bleeds. Younger children can present with only refusal to walk or use of affected joint. There is growing awareness about limitation of range of motion of joints among carriers of hemophilia and other bleeding disorders secondary to recurrent microbleeds.

• Menorrhagia: Menorrhagia is defined by either of menses lasting more than 7 days, frequent pad changes (<2 hours), or more than one period per month. Menorrhagia can result in anemia and decrease in quality of life. A pictorial blood flow assessment chart can be used to provide semiobjective assessment of menstrual blood loss. Menorrhagia in setting of underlying bleeding disorder often occurs with first cycle at menarche. The American College of Obstetrics and Gynecology recommends evaluation of VWD in women presenting with menorrhagia. Women with platelet dysfunction disorders and other coagulation disorders can also present with menorrhagia.

• Surgical bleeding: Circumcision, tonsillectomy, or wisdom teeth extraction are common surgical procedures performed in pediatric population. Surgical bleeding in bleeding disorder patients is characterized by uncontrolled bleeding during or after the procedure, bleeding that extends beyond the surgical site, unexpected need for blood transfusion, or delayed bleeding after procedure. Posttonsillectomy bleeding is usually delayed until 7–10 days after procedures in patients with underlying bleeding disorder.

• Bleeding in infancy: History of bleeding during newborn period should include cephalhematoma, umbilical cord bleeding, bleeding after heel stick, and postcircumcision bleeding.

Is Bleeding Congenital or Acquired?

In general, early presentation during newborn period or infancy points toward more severe bleeding disorder and congenital cause. In this clinical setting, the diagnosis of bleeding disorder is urgent to guide appropriate clinical management.

Family history is critical for differentiating congenital bleeding disorders from acquired disorders. X-linked inheritance pattern suggests diagnosis of hemophilia either factor VIII or factor IX deficiency. It is essential to keep in mind that approximately one-third of patients with hemophilia have a negative family history. Hereditary hemorrhagic telangiectasia and common bleeding disorders such as VWD and mild platelet function abnormalities have autosomal dominant inheritance. Common bleeding disorders can have variable clinical phenotype and can be more symptomatic in women because of the additional hemostatic challenges of menstruation and child birth.

Acquired bleeding disorder are generally due to underlying systemic illness, medication, secondary structural or functional VW deficiency, or coagulation factor inhibitor. As coagulation factors are mainly synthesized in the liver, liver dysfunction is a common cause of acquired bleeding disorder. Generally, it presents with multiple clotting factor deficiencies. Accumulation of urea and acidosis in renal failure can interfere with platelet function. Vitamin K in essential for the synthesis of multiple coagulation factors and deficiency secondary to malabsorption syndromes or antibiotics can lead to bleeding. Mechanical heart valve can lead to cleavage of VW factor by mechanical shear forces and results in acquired VWD. Adsorption of VWF on malignant cells of Wilms tumor causes acquired VWD. Medication such as aspirin, nonsteroidal antiinflammatory drugs, and others can have significant effect on platelet function. Disseminated intravascular coagulation is caused by widespread activation of coagulation cascade, which results in thrombocytopenia and consumptive coagulopathy.