Primary thrombocythemia is a myeloproliferative disorder characterized by a tendency to bleed and thrombosis, with a persistent and significant increase in peripheral blood platelets that are functionally abnormal, along with excessive proliferation of bone marrow megakaryocytes. Due to frequent recurrent bleeding, it is also known as hemorrhagic thrombocythemia. The incidence is relatively low and is more common in individuals over 40 years of age.

bubble_chart Pathogenesis

The disease cause is unknown. G6PD isoenzyme examination confirmed that this disease is also a clonal disorder of pluripotent stem cells, leading to persistent and significant proliferation of bone marrow megakaryocytes, increased platelet production, and the release of platelets stored in the spleen and liver. However, platelet lifespan is mostly normal.

The bleeding mechanism of this disease is due to platelet function defects, impaired adhesion and aggregation functions, reduced platelet factor three categories of disease cause, decreased serotonin, and abnormal release function. Some patients also have abnormal coagulation mechanisms and increased capillary fragility. Due to excessive platelets, activated platelets produce thromboxane, which easily induces platelet aggregation and release reactions, potentially forming microvascular thrombi. In the advanced stage, extramedullary hematopoiesis may occur in the spleen and other organs.

bubble_chart Clinical Manifestations

The onset is slow, and clinical manifestations vary in severity. Approximately 20% of patients, especially younger individuals, are asymptomatic at onset and are occasionally diagnosed through blood tests or the discovery of splenomegaly. Mild cases may only present with dizziness and lack of strength, while severe cases can involve bleeding and thrombosis. Bleeding is often spontaneous and may recur, occurring in about two-thirds of cases. Gastrointestinal bleeding is common, and epistaxis, gum bleeding, hematuria, and skin or mucous membrane ecchymosis may also occur, though purpura is rare. The incidence of thrombosis is lower than that of bleeding. Domestic statistics indicate that 30% of cases involve arterial or venous thrombosis. Embolism in limb vessels can lead to numbness, pain, or even gangrene, and may also manifest as erythromelalgia. Embolism in the spleen or mesenteric vessels can cause abdominal pain and vomiting. Pulmonary, cerebral, or renal embolism results in corresponding clinical symptoms. Splenomegaly occurs in 80% of cases, typically mild to grade II. A small number of patients may exhibit hepatomegaly.

(1) Blood Picture The platelet count is mostly between 1 million and 3 million/mm³, with the highest reaching 20 million/mm³. In blood smears, platelets aggregate into clumps, varying in size, with giant and畸形 forms, and occasionally, megakaryocyte fragments and bare nuclei are observed. The white blood cell count may be normal or increased, mostly between 10,000 and 30,000/mm³, generally not exceeding 50,000/mm³. The differential count shows a predominance of segmented neutrophils, with occasional immature granulocytes. In 30% of patients, the red blood cell count is normal or shows grade I增多, with variations in size and shape, polychromasia, and the possible presence of Howell-Jolly bodies and basophilic stippling. A few patients may experience repeated bleeding leading to hypochromic anemia.

(2) Bone Marrow Picture There is marked hyperplasia of nucleated cells, especially megakaryocytes, with an increase in原始 and immature megakaryocytes, and platelets aggregated in clumps. The alkaline phosphatase activity of neutrophils is increased.

(3) Bleeding and Coagulation Tests The bleeding time is prolonged, the prothrombin consumption time is shortened, clot retraction is poor, the prothrombin time is prolonged, and there is impaired thromboplastin generation. Platelet adhesion function and aggregation induced by adrenaline and ADP are reduced, but the response to collagen-induced aggregation is generally normal.

(4) Others Chromosomal analysis reveals deletion of the long arm of chromosome 21 (21q^-), and there are also reports of variable-sized abnormalities in the long arm of chromosome 21. Serum levels of acid phosphatase, potassium, calcium, phosphorus, lactate dehydrogenase, and uric acid are all increased.

For unexplained thrombocytosis (>600,000/mm³), with a significant increase in megakaryocytes in the bone marrow, combined with splenomegaly, bleeding, or thrombosis, the diagnosis of this disease should be considered. However, it must be differentiated from secondary (or reactive) thrombocytosis and other myeloproliferative disorders.

Secondary thrombocytosis is seen after splenectomy, splenic atrophy, acute or chronic blood loss, trauma, and post-surgery. Chronic infections, rheumatoid arthritis, Bi disease, necrotizing granuloma, ulcerative colitis, malignant tumors, childbirth, and drug reactions such as epinephrine can also cause thrombocytosis. It has been reported that in bone marrow cell culture, primary thrombocytosis exhibits spontaneous megakaryocyte colony formation, which can distinguish it from secondary cases.

bubble_chart Treatment Measures

The goal of treatment is to reduce platelets to normal or near-normal levels to prevent thrombosis and bleeding.

(1) Myelosuppressive drugs: Busulfan is a commonly used and effective medication, preferably administered in small doses, starting at 4–6 mg/d. If rapid platelet reduction is required, hydroxyurea at 2–4 g/d can be chosen, with the dose reduced to 1 g/d after 3–4 days. Cyclophosphamide, chlorambucil, and melphalan are also effective. The medication can be discontinued once platelet counts decrease or symptoms improve. Recurrence may warrant retreatment.

(2) Radioactive phosphorus (³²P): Administered orally or intravenously, with an initial dose of 0.08–0.11 MBq. A repeat dose may be given after three months if necessary. Its use is generally discouraged due to the potential risk of inducing leukemia.

pregnancy and childbirth, or prior to elective surgery.

(4) Interferon: Recent studies suggest the use of alpha-interferon for treating essential thrombocythemia. It inhibits megakaryocyte production and shortens platelet lifespan. The dose is 3–5 MU/d. {|107|} (5) Others: Medications such as dipyridamole, aspirin, and indomethacin can prevent platelet aggregation. Heparin or dicoumarol anticoagulants are used for thrombosis cases. Splenectomy is contraindicated.

bubble_chart Prognosis

The course of the disease varies depending on the degree of thrombocytosis. Most cases progress slowly, with a median survival often exceeding 10 to 15 years. A small number of patients may develop myelofibrosis, polycythemia vera, or chronic myeloid leukemia. Thrombosis and hemorrhage in vital organs are often the main causes of death in this condition.