bubble_chart Overview

Secondary thrombocytopenia, also known as acquired thrombocytopenia, refers to a decrease in platelets caused by other underlying diseases, involving a wide range of conditions. Examples include drug-induced immune thrombocytopenia and other immune-related thrombocytopenias such as Evans syndrome, chronic lymphocytic leukemia, various acute leukemias, lymphomas, systemic lupus erythematosus, rheumatoid arthritis, hyperthyroidism, and others.

bubble_chart Etiology

In this category of diseases, the platelet count is normal, but the ability to form clots is impaired, and bleeding time is prolonged. Abnormalities in platelet function may be due to intrinsic platelet defects or extrinsic factors that alter normal platelet function. Platelet defects can be hereditary or acquired. Tests for the coagulation phase of hemostasis (e.g., PTT and PT) are normal in most (but not all) cases.

Due to the widespread use of aspirin, which affects platelet function, acquired platelet dysfunction is common. Many other drugs can also cause platelet dysfunction. Numerous clinical conditions (e.g., myeloproliferative disorders, myelodysplastic syndromes, uremia, macroglobulinemia, multiple myeloma, cirrhosis, and systemic lupus erythematosus) can also impair platelet function.

Aspirin may slightly prolong bleeding time in normal subjects, but in patients with preexisting platelet dysfunction or severe coagulation disorders (e.g., those receiving therapeutic doses of heparin or with severe hemophilia), it can significantly prolong bleeding time. During cardiopulmonary bypass, blood flow through the pump oxygenator can lead to platelet dysfunction and prolonged bleeding time. Therefore, regardless of platelet count, platelet concentrates should be administered after cardiac surgery if there is significant bleeding and prolonged bleeding time. Platelet dysfunction appears to result primarily from activation of fibrinolysis on the platelet surface, leading to the loss of glycoprotein Ib binding sites for von Willebrand factor (VWF). Studies report that administering aprotinin (a protease inhibitor that neutralizes plasmin activity) during cardiopulmonary bypass can prevent prolonged bleeding time and reduce transfusion requirements.

Patients with uremia due to chronic renal failure may experience unexplained prolonged bleeding time. Effective dialysis, cryoprecipitate transfusion, or desmopressin administration can temporarily shorten bleeding time. Transfusion of red blood cells or administration of erythropoietin to increase red blood cell counts can also reduce bleeding time.

bubble_chart Clinical Manifestations

1. Drug-induced immune thrombocytopenia: There is a latent period before the onset of bleeding symptoms. In short cases, symptoms may appear within hours of taking the medication, while in longer cases, symptoms may appear months later. The typical range is 5 to 10 days. It is often accompanied by fear of cold, fever, headache, nausea, vomiting, etc.
2. Other immune thrombocytopenias: Patients exhibit generalized skin purpura, epistaxis, or hypermenorrhea in women, fatigue, pale complexion, and darkened urine. Occasionally, signs of kidney damage such as hypertension, hematuria, and azotemia may also be observed. Neurological symptoms are very rare.
3. Hemorrhagic and coagulation disorders
   1. Aplastic anemia and bone marrow nature of disease diseases: All types of aplastic anemia caused by various factors share characteristics such as reduced megakaryocytes in the bone marrow and decreased platelet production. Thrombocytopenia may be the earliest manifestation of aplastic anemia or may persist even after treatment when hemoglobin and granulocytes have returned to normal. In bone marrow nature of disease diseases such as cancer infiltration, thrombocytopenia mostly occurs due to tumor cells damaging megakaryocytes, leading to reduced platelet production. Both conditions can be diagnosed definitively through bone marrow examination. In the former, bone marrow hypoplasia and reduced megakaryocytes are observed, while in the latter, tumor cells can be detected.
   2. Suppression of bone marrow by physicochemical factors: Physicochemical factors such as ionizing radiation, alkylating agents, antimetabolites, and cytotoxic agents commonly cause thrombocytopenia as a complication during the treatment of malignant tumors, either by directly poisoning bone marrow cells or by triggering immune reactions. These factors mostly cause diffuse injury to the bone marrow, presenting as pancytopenia in patients. However, in a few patients, megakaryocytes are more sensitive to radiation, so some may exhibit only thrombocytopenia and reduced megakaryocytes.
   3. Factors selectively inhibiting megakaryocytes: Chlorothiazide drugs and their synergists can cause thrombocytopenia, not only through the mechanism of producing platelet antibodies but also by inhibiting platelet production, with the latter being more significant. This is generally considered a pharmacological effect. Patients present with bone marrow suppression and reduced megakaryocytes. In mild, asymptomatic cases, up to 25% of patients taking this medication may be affected. In rare cases, pregnant women taking this drug may give birth to newborns with congenital thrombocytopenia, while the mother remains asymptomatic.
   4. Congenital megakaryocytic hypoplasia: This rare condition is characterized by significantly reduced megakaryocytes and platelets, often accompanied by congenital malformations such as in the kidneys, heart, or bones. The prognosis is poor, with about two-thirds of affected infants dying from intracranial hemorrhage within 8 months. Maternal rubella during pregnancy or oral D860 intake may be contributing factors.
   5. Others: Estrogen may occasionally cause amegakaryocytic thrombocytopenia. Ethanol can inhibit platelet production, which is a relatively common cause of thrombocytopenia in patients who consume large amounts of alcohol over a long period. Clinical bleeding manifestations are rare, and platelets may recover after cessation of alcohol consumption.
4. Ineffective platelet production: This condition is commonly seen in some patients with megaloblastic anemia due to vitamin B12 or folate deficiency. It presents as thrombocytopenia, with some patients showing bleeding tendencies and others exhibiting pancytopenia. Bone marrow megakaryocytes are normal or even increased, indicating ineffective platelet production. Platelet counts may normalize with treatment of the megaloblastic anemia.
5. Thrombopoietin deficiency: This disease is caused by congenital thrombopoietin deficiency, leading to thrombocytopenia. It is mostly hereditary, with bleeding manifestations beginning in infancy. Platelet counts are reduced, while megakaryocyte numbers are normal, with no special changes in morphology or structure.
6. Cyclic Thrombocytopenia: This disease is a hemorrhagic disorder caused by unexplained periodic thrombocytopenia. It is relatively common, with thrombocytopenia alternating with thrombocytosis or normal platelet counts at regular intervals, typically every 20 to 30 days. The condition is more prevalent in women, and its episodes often coincide with menstruation, during which thrombocytopenia occurs and bleeding increases. Megakaryocytes are generally not reduced, with skin and mucous membrane bleeding being the main manifestations. There is no specific treatment.
7. Thrombocytopenia caused by spleen disease: Under normal circumstances, one-third of the platelets in the body reside in the spleen. When splenomegaly occurs, such as in portal hypertension, Gaucher's disease, lymphoma, sarcoidosis, or Folty syndrome, the platelet count may decrease, but the total amount of platelets in the body does not decrease. After injection: Epinephrine can significantly increase the platelet count within a certain period. Sometimes, there may also be factors that simultaneously increase platelet destruction.
8. Infectious thrombocytopenia: This disease is a thrombocytopenic bleeding disorder caused by viruses, bacteria, or other infections.
   1. Viral infections: Viral infections that can lead to thrombocytopenia include measles, rubella, herpes simplex, chickenpox, cytomegalovirus infection, viral hepatitis, influenza, mumps, infectious mononucleosis, epidemic hemorrhagic fever, cat scratch fever, and dengue fever. Viruses can invade megakaryocytes, reducing platelet production. Viruses can also adhere to platelets, increasing platelet destruction. In some severe measles patients and those with epidemic hemorrhagic fever, platelets are consumed due to disseminated intravascular coagulation.
   2. Bacterial infections: Many bacterial infections can cause thrombocytopenia, including Gram-positive and Gram-negative bacterial sepsis, meningococcal meningitis, bacteremia, cold-damage disease, subcutaneous nodule disease, bacterial endocarditis, scarlet fever, and brucellosis. Bacterial toxins inhibit platelet production or increase platelet destruction. They may also increase platelet consumption by affecting vascular wall function.
   In summary, for patients with isolated thrombocytopenia and clear signs of infection, this disease should be considered. Platelet levels typically recover after the primary infection is controlled.

bubble_chart Auxiliary Examination

1. Significance of bleeding time (BT) measurement: Prolonged bleeding time is seen in structural or functional abnormalities of blood vessels, such as scurvy, telangiectasia, and von Willebrand disease.
   1. Abnormal platelet counts: such as thrombocytopenic purpura due to various causes and thrombocytosis.
   2. Abnormal platelet function: such as thrombocytopathy and thrombasthenia.
   3. Others: such as hypo-/afibrinogenemia, primary and secondary fibrinolysis, and the presence of anticoagulants in the blood circulation.
2. Significance of aspirin tolerance test: This test is an important method for diagnosing von Willebrand disease, as mild cases may still have normal bleeding time, but prolonged bleeding time can be observed after taking aspirin.
3. Significance of capillary fragility test: More than 10 new bleeding spots indicate a positive result, suggesting increased capillary fragility, which can be seen in the following conditions:
   1. Abnormalities of the capillary wall: such as hereditary hemorrhagic telangiectasia, allergic purpura, scurvy, and infectious vascular purpura.
   2. Decreased platelet count: such as primary or secondary thrombocytopenic purpura.
   3. Platelet function defects: such as thrombasthenia, thrombocytopathy, and acquired platelet function defects caused by drugs or certain diseases.
4. Significance of von Willebrand factor (VWF) measurement: Decreased VWF is seen in von Willebrand disease and hemophilia carriers. Increased VWF is seen in:
   1. Endothelial injury: such as ischemic cardiovascular and cerebrovascular diseases, peripheral vascular diseases;
   2. Hypercoagulable states: such as nephrotic syndrome, pregnancy-induced hypertension, uremia, etc.;
   3. Others: such as after major surgery, diabetes, hyperlipidemia, DIC, etc.
5. Significance of 6-keto-prostaglandin F1a (PG F1a) measurement: Decreased 6-keto-prostaglandin is seen in
   1. Congenital platelet arachidonic acid metabolism defects or after taking nonsteroidal anti-inflammatory drugs such as aspirin;
   2. Hypercoagulable states and thrombotic diseases, such as coronary heart disease, cerebral arteriosclerosis, cerebral thrombosis, diabetes, glomerulopathy, peripheral vascular thrombosis, etc.

bubble_chart Treatment Measures

1. Since the thrombocytopenia in this disease is secondary, treating the primary disease is crucial, and platelet counts often improve correspondingly as the primary condition resolves.
2. The etiology of this disease is complex and can involve poisoning, drug allergies, infections, autoimmune disorders, dyslipidemia, genetic factors, etc. Western medicine currently lacks specific treatments, making early application of Chinese medicine therapy essential.