3.3.2 Management Considerations
Without treatment, KLA commonly progresses and causes hemorrhage,
effusions, cardiorespiratory compromise, multiorgan failure or even
death. Unfortunately, there is no cure for KLA. Goal of therapy is to
halt disease progression, control coagulopathy, manage symptoms and
prevent complications. Currently, no universal guidelines exist for the
treatment of KLA. KLA typically cannot be completely removed with
surgery because of its infiltrative and multifocal nature and should be
avoided given the high bleeding risk. Various medical therapies such as
steroids, single or multiple chemotherapy agents, interferon, and
sirolimus, have been used [9, 25-27]. Often used in combination as
2-drug or 3-drug regimens, oral sirolimus, intravenous or oral steroids,
and vincristine, have become the preferred agents in the initial
treatment of KLA [16]. Refer to Table 2 for suggested treatment
regimen(s).
Bleeding complications are common in patients with KLA, but blood
product replacement must be performed with caution. Platelet
transfusions can worsen the underlying coagulopathy and oftentimes, does
not improve platelet counts. Platelet transfusions should only be given
for active, uncontrolled bleeding or immediately prior to or during a
procedure with more than low risk for bleeding [27]. Fresh frozen
plasma (FFP) or cryoprecipitate is recommended for hypofibrinogenemia
less than 100 mg/dL. Prior to any procedure with more than minimal to
low risk of bleeding and in patients with active bleeding, fibrinogen
should be corrected to greater than 150 mg/dL. RBC transfusions do not
have any negative effect on KLA, so should be given to maintain
oxygenation, perfusion and symptomatic relief.
In our patient, platelet transfusions worsened her hypofibrinogenemia
and failed to improve her thrombocytopenia. This is an expected
phenomenon occurring because of increased platelet trapping in the KLA
lesions and subsequent activation of the coagulation cascade. She was
initially started on sirolimus but due to intolerable side effects was
switched to the MEK inhibitor, trametinib. Her hematologic parameters
normalized on sirolimus, and her disease remains controlled on
trametinib.