A Systematic Approach to the Bleeding Patient: Correlation of Clinical Symptoms and Signs With Laboratory Testing

Introduction

In the current medical climate of laboratory expertise and automation, an expanded menu of increasingly sophisticated testing can provide immediately meaningful diagnostic, therapeutic, and prognostic indicators. On the other hand, economic justification and insurance “gatekeeping” often constrain the physician's ability to obtain these data. The clinical hematologist/hemostaseologist is particularly affected due to the number of esoteric laboratory assays required to provide state-of-the-art and cost-effective patient management. Examination of the peripheral blood smear and bone marrow aspirate to establish a diagnosis based on visual and morphologic criteria has been supplanted by considerably more accurate and sensitive immunohistochemical, cytogenetic, molecular diagnostic, and flow cytometric analyses with monoclonal antibodies. In contrast, and perhaps more unique to the bleeding patient than to other categories of illness, the patient interview provides the foundation for making the diagnosis, determining which laboratory tests are most appropriate to order, and formulating treatment strategies. Careful attention to these elements of patient assessment substantially reduces morbidity, mortality, and the cost of care while minimizing the medical-legal exposure of the physician.

This chapter offers a systematic approach to the patient with a clinically significant risk of bleeding or an immediate history of spontaneous excessive hemorrhage. Approaches to laboratory confirmation of bleeding causes are also presented, because interpreting data from the coagulation laboratory requires an understanding and appreciation of the vagaries of the techniques employed to generate them. This chapter also discusses how the coagulation laboratory can provide insight into the pathophysiology of the patient's condition and presents a rationale for treatment.

Evaluating patients with hemorrhagic complications is a multistep process involving a complete history, detailed physical examination, and directed laboratory evaluation. The relative emphasis placed on each of these components varies according to the unique clinical situation, but all factors must be considered. Important points of differentiation include localized versus systemic defects, acquired versus inherited defects, and disorders of primary (i.e., those related to platelet abnormalities) versus secondary hemostasis (i.e., those related to coagulation factor, fibrinogen, or connective tissue abnormalities). It is important for the clinician to understand that some clinical situations do not allow for a comprehensive evaluation and may therefore require a more streamlined approach. Intubated patients who develop brisk bleeding during the immediate postoperative period, for example, will be unable to provide any information about their personal or family history; a determination of these patients' most likely cause for bleeding will therefore rest on pertinent physical and laboratory findings. Of primary importance for all consulting hematologists is realizing that the management of coagulation abnormalities—which are often epiphenomena or complications of other medical illnesses—is often empirical and cannot always be approached through a standard algorithm.

Clinical Evaluation

Each component of the clinical assessment provides critical information supporting or refuting the possibility that a true hemorrhagic disorder exists. The information garnered from the history and physical examination ultimately guides the direction, extent, and tempo of the laboratory evaluation and helps the clinician determine how future bleeding complications can be managed and/or prevented. This multifactorial approach is necessary because the likelihood of false-positive and false-negative diagnoses is high when the decision rests on one component alone. Consider, for example, the process required to obtain an accurate medical history. Patients' perception of their own bleeding tendency is often exaggerated or understated. In one study conducted in the Åland Islands, where von Willebrand disease (VWD) was originally detected in 1928, 65% of women and 35% of men from families with no history of bleeding and no personal laboratory evidence of a bleeding disorder answered a self-administered binary questionnaire with responses indicative of a symptomatic bleeding diathesis. In contrast, 38% of the women and 54% of the men with documented laboratory evidence of a coagulation defect and a positive family history of symptomatic VWD or qualitative platelet disorders answered the same questionnaire as if they were completely unaware of their bleeding diathesis.