Page 2522 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 154 Hematologic Manifestations of Renal Disease 2245

risk of venous and arterial thrombosis was 1% and 1.5% per year, treatment with intravenous fluids, platelet and red blood cell transfu-
respectively, which is about eight times greater than the general popu- sions, and hemodialysis as indicated for acute kidney injury (AKI).
lation. 24,25 There are certain high-risk factors for developing venous
thromboembolism (VTE), including degree of hypoalbuminemia
as well as type of nephrotic syndrome (membranous nephropathy HEMATOLOGIC ABNORMALITIES IN THE RENAL
being the highest risk). 26,27 The mechanism of hypercoagulability TRANSPLANT PATIENT
is multifactorial and involves all stages of hemostasis. Nephrotic
syndrome patients have increased platelet aggregation and adhesion Several hematologic abnormalities can occur in the renal transplant
because of elevated levels of vWF and unbound arachidonic acid patient, including posttransplant lymphoproliferative disorder
(usually albumin bound). 28,29 There is also increased activation of the (PTLD), posttransplant erythrocytosis (PTE), and acquired TMA
coagulation cascade caused by an imbalance between synthesis and secondary to drugs or infection. PTLD is a rare complication in organ
urinary loss of thrombotic and antithrombotic factors. For certain transplant recipients. PTLD is caused by proliferation of Epstein-Barr
plasma proteins, including factor XII, antithrombin, and free protein virus (EBV)–infected B cells because of reduced T-cell surveillance as
S, urinary losses exceed synthesis. 30–32 For higher-molecular-weight a result of immunosuppression. PTLD may present along a spectrum
proteins, including factors V, VIII, vWF and fibrinogen, excess of disease, from an infectious mononucleosis like syndrome (early
synthesis relative to losses lead to accumulation. 33,34 Decreased lesions), polyclonal lymphoid hyperplasia (polymorphic PTLD), to
fibrinolysis also occurs because of reduced plasminogen levels and monoclonal malignancies including B- or T-cell lymphoma (mono-
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reduced availability of albumin as a cofactor for plasminogen–fibrin morphic PTLD). Among renal transplant recipients, one study
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interaction. 35,36 demonstrated an incidence of 1.4% (344) out of 25,127 patients.
The management of thromboembolic events (renal vein throm- Risk factors for the development of PTLD include the use of T–cell
bosis, deep venous thrombosis [DVT], pulmonary embolism [PE]) depleting induction agents, EBV-negative recipient with positive
associated with nephrotic syndrome is similar to conventional anti- donor, history of pretransplant malignancy and younger age. Treat-
coagulation strategies for DVT or PE, with the use of heparin, low- ment of PTLD includes a reduction in immunosuppression for all
molecular-weight heparin, warfarin or direct oral anticoagulant types, with the addition of rituximab for polymorphic PTLD. Che-
37
agents many of which require renal dose adjustment. The direct motherapy is used in monomorphic PTLD and also for a subset of
thrombin and factor Xa inhibitors have a variable degree of renal patients with polymorphic disease. 42
clearance, with Dabigatran being the most and Apixiban being the Posttransplant erythrocytosis is defined as an elevated hemoglobin
37a
least renally cleared. These agents, however, have not been studied and hematocrit after renal transplantation that persists for more than
38
specifically in patients with VTE related to nephrotic syndrome. In 6 months in the absence of another cause. PTE occurs in about 10%
terms of duration of therapy, most experts recommend continuing to 15% of transplant recipients and is thought to be multifactorial,
37
anticoagulation as long as the patient remains nephrotic. Prophy- potentially related to unregulated erythropoietin secretion from the
lactic anticoagulation for patients with nephrotic syndrome is a native kidneys. As with other forms of erythrocytosis, patients may
controversial issue and must be balanced with the risk of bleeding. experience headache, lethargy, plethora and are at increased risk for
Some experts recommend prophylactic anticoagulation in patients thromboembolic events. Treatment consists of blockage of renin
who are high risk for VTE (membranous nephropathy, albumin angiotensin aldosterone system, through ACE inhibitor or ARB
<20 g/L) with low to intermediate risk of bleeding. 37 therapy. 44
HEMOLYTIC UREMIC SYNDROME REFERENCES

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viral infections. The kidney plays a central role in all of these 8. Portolés J, Torralbo A, Martin P, et al: Cardiovascular effects of recom-
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anemia. 40 compared with low hematocrit values in patients with cardiac disease
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