118 Hereditary and Reactive Thrombocytosis

Question 1

The causes of thrombocytosis in which the platelet count exceeds the upper limit can be broadly categorized as:

Answer 1

• Clonal, including essential thrombocythemia and other myeloproliferative neoplasms
• Familial
• Reactive or secondary

Question 2

The ligand for the megakaryocytic growth factor receptor c-MPL, is the major humoral regulator of megakaryocyte survival, growth, and development

Answer 2

Thrombopoietin (TPO)

It does not stimulate the final step in thrombopoiesis: platelet release from megakaryocyte proplatelet processes.

The levels of TPO inversely related to platelet counts

Question 3

Produces approximately half of all the hormone that circulates (TPO)

Answer 3

Liver

Marrow stromal cells also produce TPO and are responsive to platelet products, which serve to downmodulate expression of the hormone.

Question 4

TRUE OR FALSE

Platelet levels affect hepatic TPO production

Answer 4

FALSE

Platelet levels do not affect hepatic TPO production

Instead, platelets themselves have an important role in regulating plasma levels, because their receptors for TPO (c-MPL) remove it from plasma.

Question 5

Receptor where senescent platelets bind and lead to stimulation of hepatocyte signaling pathways and subsequent expression of TPO

Answer 5

Ashwell-Morell hepatocyte receptor

Question 6

The most common cause of secondary thrombocytosis

Answer 6

Inflammation

The most common diagnoses in such patients are inflammatory bowel disease and rheumatoid arthritis, although most conditions in which the erythrocyte sedimentation rate or C-reactive protein is elevated have been reported to cause secondary thrombocytosis.

Question 7

Cytokines most closely associated with thrombocytosis

Answer 7

IL-6 and IFN-γ

Question 8

Key regulator of the inflammatory response

Stimulate the hepatic production of TPO

Answer 8

Interleukin-6

Question 9

Stimulates megakaryocyte growth and differentiation

Likely related to its stimulation of signal transducer and activator of transcription (STAT)-1 in megakaryocytes

opposite sa RBC

Direct suppression of erythroid colony-forming cell growth and the activation of macrophages to secrete a number of inflammatory cytokines

Answer 9

IFN-γ

Question 10

TRUE OR FALSE

TPO levels in patients with iron deficiency and thrombocytosis are not elevated.

Answer 10

TRUE

TPO levels in patients with iron deficiency and thrombocytosis are not elevated.

In contrast, erythropoietin (EPO) levels are elevated in patients with iron-deficiency anemia and are thought by some to be responsible for the thrombocytosis seen in iron deficiency, at least in part.

Rather, megakaryocytic progenitors display EPO receptors, and their binding of the hormone leads to many of the same intracellular biochemical signals as induced by TPO.

Question 11

TRUE OR FALSE

Although pathologic thrombosis is a major feature of primary thrombocythemia, it is virtually absent in reactive thrombocytosis, unless provoked by other features of the underlying condition (eg, vasculitis) or completely unrelated conditions in the patient (eg, atherosclerotic disease).

Answer 11

TRUE

Although pathologic thrombosis is a major feature of primary thrombocythemia, it is virtually absent in reactive thrombocytosis, unless provoked by other features of the underlying condition (eg, vasculitis) or completely unrelated conditions in the patient (eg, atherosclerotic disease).

Treatment of the thrombocytosis per se is not recommended in patients with reactive thrombocytosis, unless the patient has other significant risk factors for thromboembolic disease

Question 12

Mutations that cause familial thrombocytosis

Answer 12

Mutations in THPO (the official designation for the TPO gene) or C-MPL