CASE HISTORY • Part 1
A 46-year-old woman presents with a complaint of more than 3 months of fatigue and dyspnea on exertion. Her history is notable for lifelong recurring epistaxis, requiring repeated nasal packing, septal dermoplasty, and laser therapy. Her father also had repeated epistaxis; he died at age 60 from a brain abscess. Examination is notable for pallor and multiple blue-red lesions involving the lips and fingers. The remainder of the examination is benign except for a positive test for occult blood in the stool.
CBC: Hemoglobin/hematocrit - 7 g/dL/22%
MCV - 64 fL MCH - 24 pg MCHC - 24 g/dL
RDW-CV - 24% WBC count - 6,500/μL
Platelet count - 410,000/μL SMEAR MORPHOLOGY
Microcytic, hypochromic with marked aniso- and poikilocytosis, polychromasia, and the occasional cigar-shaped cell. White blood cells and platelets are both normal.
Reticulocyte count/index - 1.3%/<1.0 Questions
A vessel wall defect, either intrinsic or induced by trauma or inflammatory changes, can result in abnormal bleeding despite an otherwise normal coagulation system. Since there are no reliable clinical tests of vascular integrity, the diagnosis of an abnormality in vascular structure often depends on keen observation. For example, multiple small telangiectases on the lips can be a tip-off to the diagnosis of hereditary hemorrhagic telangiectasia. In patients with a normal platelet count, normal coagulation studies, and normal platelet function, the presence of petechiae, purpura, or excessive bleeding after minor trauma or surgery also must raise the question of an underlying vascular defect.
NORMAL VESSEL FUNCTION
Blood vessels provide a critical balancing act to contain and promote liquid blood flow, and at the same time resist thrombus formation. As illustrated in Figure 30-1, there is an organized structure to the blood vessel wall that serves these functions. Endothelial cells that line the blood vessels provide much more than a simple barrier to prevent the escape of blood cells. The endothelial cell is very active metabolically, synthesizing mediators of the interaction between blood components and the vessel wall. Some of these, such as prostacyclin (PGI2), nitric oxide, heparan sulfate, tissue plasminogen activator (t-PA), thrombomodulin, tissue factor pathway inhibitor (TFPI), and ADPase act to maintain blood in its fluid state by counter-acting platelet activation, aggregation, and clot formation, whereas others are primed and positioned to enhance blood procoagulant function should trauma or some other event produce bleeding (Table 30-1).
Vessel wall structure and function. Endothelial cells of the vessel wall play an important role in hemostasis. They produce inhibitors of platelet activation, including ADPase, prostacyclin, and nitric oxide. They also play a role in counteracting clot formation by providing thrombomodulin, heparan sulfates, and tissue plasminogen activator. Nitric oxide and prostacyclin produced by ...