What is known about the risk of cerebrovascular complications in patients with hematological diseases?

Dr. Amankulor: The biggest issue is the enormous risk of brain hemorrhage with hematological malignancies, which can cause bleeding in multiple ways. With multiple myeloma, for example, abnormal plasma cells crowd out space in the bone marrow and it doesn’t have the capacity to produce the cells that seal bleeding.

The mechanism is similar with leukemias, especially during the acute phase with the expansion of massive tumor cells within the circulating blood volume. Not only is there a reduction in the proportion of cells that are necessary to stop bleeding, but there is also an increase in factors secreted in the liver that lead to the coagulation cascade.

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In addition, hematological malignancies require chemotherapy that can lead to iatrogenic consequences including bleeding, as chemotherapy kills megakaryocytes.

Once the platelet count gets below around 25,000/µL, there is a risk of spontaneous bleeding, which can be catastrophic because there are not enough platelets to clot the blood. This is also where the neurosurgery part comes into consideration with the decision to actually go in and relieve the bleeding if it becomes clinically relevant. With a subdural hematoma, for example, more than a centimeter of new blood will shift the brain within the skull and increase intracranial pressure, leading to potentially catastrophic consequences, including death.

We can give patients platelets and factors derived from donors to try to normalize those they may be missing. However, depending on the degree of hematologic malignancy, the platelets might not work – as in a patient with immune thrombocytopenia, for example. In some cases, we can’t get the platelets high enough to do an operation because there is an intrinsic loss of coagulation. We generally say that the platelet count needed to do an operation, especially in the brain, is around 75,000 to 100,000/μl.

In addition to hemorrhagic strokes, there is also a risk of ischemic and thrombotic stroke in patients with hematologic malignancies, some of which cause extra clotting vs not enough clotting factors. In summary, there are 2 pathways to cerebrovascular accidents in these patients: decreased clotting or increased clotting.

What are some of the top risk factors for such events in this population?

Dr. Amankulor: There are a couple of major risk factors, including the type and stage of the malignancy. Patients with AML and different types of acute leukemias have the highest rates of stroke at the onset of the disease due to a rapid proliferation of leukemic cancer cells within the circulating blood, which can cause thrombosis.1,4,5

The type of treatment the patient receives can be another risk factor. Chemotherapy tends to cause hemorrhagic strokes because it leads to a loss of clotting factors and platelet production. That’s why these patients are monitored very closely and get blood work monthly or bimonthly so that we remain aware of their platelet counts.