From the Guidelines
Elevated D-dimer levels in patients with sickle cell disease (SCD) are significant as they indicate ongoing hypercoagulability and increased risk of thrombotic complications, though they have limited diagnostic utility for acute events. D-dimer, a fibrin degradation product, is chronically elevated in SCD patients even at baseline due to the disease's inherent hypercoagulable state, chronic hemolysis, and ongoing vascular inflammation 1. This baseline elevation makes D-dimer less useful as a screening tool for acute thrombotic events like pulmonary embolism or deep vein thrombosis in SCD patients, unlike in the general population where normal D-dimer levels can effectively rule out thrombosis.
Some key points to consider when evaluating D-dimer levels in SCD patients include:
- The chronic elevation of D-dimer in SCD patients due to the disease's pathophysiology
- The limited utility of D-dimer as a diagnostic tool for acute thrombotic events in SCD patients
- The importance of interpreting D-dimer results in the context of individual patient baseline values and clinical presentation
- The need for a comprehensive diagnostic approach that includes clinical assessment, imaging studies, and other laboratory markers
When evaluating SCD patients for potential thrombotic complications, physicians should rely more heavily on clinical assessment, imaging studies, and other laboratory markers rather than D-dimer alone to guide diagnostic and treatment decisions 1. Serial measurements showing significant increases from a patient's baseline may be more informative than single readings.
In terms of management, hydroxyurea is recommended as first-line therapy for patients with SCD who have an increased risk for mortality, as defined by a tricuspid regurgitant jet velocity (TRV) equal to or greater than 2.5 m/second, an NT-pro-BNP level equal to or greater than 160 pg/ml, or RHC-confirmed PH 1. However, the use of PAH-targeted therapy in SCD patients with PH is more nuanced and should be guided by cardiac catheterization results and individual patient characteristics 1.
From the Research
Significance of Elevated D-dimer Levels in Sickle Cell Disease
- Elevated D-dimer levels are a common finding in patients with sickle cell disease (SCD), indicating increased thrombin activity and fibrin formation 2, 3.
- Studies have shown that D-dimer levels are higher in patients with SCD during vaso-occlusive crises and other complications, such as leg ulcers, chronic cholecystitis, and aseptic necrosis 2.
- The presence of elevated D-dimer levels in SCD patients is associated with an increased risk of clinical complications, including stroke, retinopathy, and acute chest syndrome 4.
- The association between D-dimer levels and clinical complications in SCD suggests that coagulation activation may contribute to the pathophysiology of these complications 4.
Mechanisms of Elevated D-dimer Levels in Sickle Cell Disease
- The elevated D-dimer levels in SCD are thought to result from increased thrombin activity and fibrin formation, which are features of the disease 3.
- The cellular components of blood, including phosphatidylserine-expressing erythrocytes, may contribute to enhanced thrombin generation in SCD 5.
- Acquired protein S deficiency, which is common in SCD, may also contribute to the elevated D-dimer levels 5.
Clinical Implications of Elevated D-dimer Levels in Sickle Cell Disease
- The measurement of D-dimer levels may be useful as a marker for the presence of complications in SCD patients 2.
- The association between D-dimer levels and clinical complications in SCD suggests that monitoring D-dimer levels may be useful in identifying patients at high risk of these complications 4.
- Further research is needed to evaluate the contribution of coagulation and platelet activation to clinical complications in SCD and to determine the clinical utility of measuring D-dimer levels in these patients 4, 6.