Page 2552 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 157 Hematologic Manifestations of HIV/AIDS 2275

tuberculosis, CMV or hepatitis C should be excluded before initiating and additional assays will often detect an inhibitor to the protease.
treatment with corticosteroids. IVIg and anti-RhD are equally effec- First-line therapy is daily plasma exchange until remission and
9
tive in increasing platelet counts acutely in severely affected patients, maintenance of platelet count at 150 × 10 /L, though there are a
but a crossover study clearly demonstrated a longer duration of number of reported differences in how to use plasma exchange in the
response with the latter agent. management of this disorder. Initial plasma exchanges should be at
Splenectomy has proven to be safe and effective in refractory least a 1.5 plasma volume exchanges. Corticosteroids such as predni-
patients with HIV-TP. After splenectomy, there is a transient increase sone (1 mg/kg/day) can also be given with the exchanges. If plasma
in the peripheral blood CD4 lymphocyte count, which reflects exchange is not immediately available, infusion of fresh frozen plasma
redistribution from the splenic pool into the circulation rather than alone has been shown to be effective in patients with HIV-associated
an improvement in the patient’s immunologic status. TTP. In classic TTP, relapses can occur in up to 30% of patients;
HIV-related hematologic cytopenias have been shown to correlate however, relapse in HIV-associated TTP appears to be less frequent.
with plasma viral load. Effective antiretroviral therapies have resulted Patients who relapse can be treated with repeat exchange combined
in improvement in several HIV-related cytopenias, including HIV- with immunosuppressive therapy including such agents as vincristine
CITP. Zidovudine monotherapy increased platelet counts in 60% to or rituximab.
70% of HIV-CITP patients. Although other antiretroviral drugs have HUS most likely results from endothelial perturbation secondary
been shown to improve hematologic parameters in patients with to either HIV or other viral infections such as CMV, drug or toxin
advanced HIV infection, their efficacy as monotherapy for the induced such as observed with Escherichia coli 0157:H7 infection.
management of HIV-CITP is less well documented. Use of HAART Recent data suggest that the primary event leads to unregulated
in both de novo and zidovudine-refractory HIV-CITP has induced complement activation caused either by inhibitors of complement
sustained platelet responses in association with effective viral regulatory protein such as complement H or congenital abnormalities
suppression. in complement regulation. In these patients, measurement of
Responses to zidovudine and HAART may be more limited in ADAMTS13 activity will uniformly report levels near normal and
HIV-infected intravenous drug users, possibly reflecting the impact above 30%. Many patients will respond to aggressive plasma exchange,
of associated liver disease and infection with hepatitis C virus (HCV). but complete remissions are rare. Recently the inhibitor of comple-
In a prospective placebo-controlled, double-blind, randomized trial, ment C5a, eculizumab, has been approved for the treatment of
12 of 14 zidovudine refractory HIV-infected intravenous drug users atypical HUS, but there are no reports of its use in HIV-associated
with elevated serum alanine aminotransferase suggestive of underly- HUS.
ing liver disease who were treated with IFN-α had a statistically sig-
nificant increase in their platelet counts by week 4 of therapy. Similar
responses to IFN-α therapy alone have been reported in HIV- THROMBOEMBOLIC DISEASE
seronegative, HCV infected patients. An open label trial of IFN-α in
a cohort of predominantly homosexual men documented responses Since the beginning of the AIDS epidemic, an unexpectedly high
in nine of 16 patients, with responses occurring as early as 2 weeks incidence of venous thromboembolism (VTE) has been observed
after the initiation of treatment. Such rapid responses preclude the among people with HIV disease. The most compelling data in
possibility that improvement in the platelet count is solely caused by support of an increased risk of VTE in HIV disease estimated the
suppression of concomitant HCV infection. At present, there are no incidence of thrombosis in their HIV-infected population to be about
data evaluating the efficacy of the new approved thrombopoietin 2.6 per 1000 person-years. Given the fact that cohorts of patients
receptor agonists, romiplostim and eltrombopag, in the management with HIV infection tend to include a disproportionate number of
of HIV-related thrombocytopenia, but long-term efficacy and safety younger individuals compared with the general population, this
data regarding the use of these agents in primary ITP would suggest figure represents an increased incidence of VTE. The increased
that they would be effective in the management of HIV-associated incidence in venous thrombosis was disproportionately greater among
ITP. patients with clinical AIDS, those older than 45 years, those with
AIDS-defining illnesses (particularly CMV infection), and those
THROMBOTIC MICROANGIOPATHY AND THROMBOTIC taking indinavir (Crixivan) or megestrol acetate (Megace). However,
53% of the thrombotic events occurred in individuals without history
THROMBOCYTOPENIC PURPURA of recent hospitalization.
In a study comparing the risk of VTE in HIV-infected patients
Thrombotic microangiopathy including both TTP and the hemolytic to an age-matched uninfected control population, there was no sta-
uremic syndrome (HUS) is a well-described complication of HIV tistic difference in the overall risk of VTE (2.8% HIV-infected versus
infection seen in approximately 1% of patients. The incidence of this 1.8% controls) except in the HIV-infected patients less than 50 years
complication appears to have decreased with the advent of HAART. (3.31% HIV-infected versus 0.53% controls; p < .0001). A study of
The incidence of TTP appears to be similar to that observed in the 37,535 HIV-infected veterans compared with 37,535 age, race and
general population, whereas HUS appears frequently in patients with site-matched uninfected controls found in evidence that a 39%
advanced HIV infection. increased incidence in VTE in the pre-HAART era (before 1996) and
TTP can occur any time in the course of HIV infection and has a 33% increased incidence in the era of HAART. The increased risk
been reported in some patients to be the initial manifestation of HIV of thrombosis was independent of a diagnosis of malignancy, HIV-
infection. This life-threatening disorder is characterized by thrombo- related opportunistic infections, or the use of central catheters. The
cytopenia and microangiopathic (fragmentation) hemolytic anemia. development of a thromboembolic event was associated with a sta-
The original description of this disorder emphasized a classic pentad tistically increased mortality in all groups.
of fever, thrombocytopenia, microangiopathic hemolytic anemia,
renal failure, and neurologic abnormalities. However, most patients
present with only one or two manifestations of the original pentad Role of Inflammation and Its Effect on the Protein C
and isolated thrombocytopenia may be the initial finding. Therefore and S Anticoagulant System
it is essential that the evaluation of thrombocytopenia includes a
careful review of the peripheral blood smear. With advancing HIV disease, there are progressive prothrombotic
TTP is the result of a failure to process endothelial derived high hemostatic changes, specifically a decrease in protein S and an increase
molecular weight von Willebrand factor caused by an absence of/or in factor VIII. There is a well-documented association between acute
inhibitor to the von Willebrand factor cleaving protease (AD- and chronic inflammation and activation of the hemostatic system.
AMTS13). Measurement of ADAMTS13 activity before the initia- Inflammatory cytokines such as TNF-α, IL-1, and IL-6 have been
tion of plasma exchange will report levels nearly always less than 10% shown to activate coagulation and downregulate activation of protein