Thrombocytes are responsible for the initial wound closure in the course of primary hemostasis. If there is a deficiency in this system bleeding time is significantly prolonged after an injury. The causes are frequent and have a wide spectrum. Regarding differential diagnosis, one has to consider different (malignant) underlying diseases. You should memorize the classification scheme for your future medical occupation!
Thrombocytopenia blood film

Image: "A film from a thrombocytopenic patients. Almost devoid of platelets." by Prof. Erhabor Osaro. License: CC BY-SA 4.0

You may find a general overview about blood disorders in the article ‘Hemostaseology: Differential Diagnosis of Blood Disorders’.

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Definition, Etiology and Pathophysiology of Thrombocytopenia

Thrombocytopenia blood film

Image: “A film from a thrombocytopenic patients. Almost devoid of platelets.” by Prof. Erhabor Osaro. License: CC BY-SA 4.0

Thrombocytopenia describes a deficiency in thrombocytes in peripheral blood. Thrombocytes are functionally integrated into the hemostasis system. Thus, thrombocyte function disorders cause pathological bleedings. In the spectrum of hemorrhagic diatheses, this group of coagulopathy is the main cause for pathological bleedings.

How does a disorder in thrombocyte cell count develop? Like at almost all bleeding disorders, the causes can be divided into disturbed synthesis or increased peripheral turnover.

Thrombocytopenia due to synthesis disorders

Decreased thrombocytopoiesis can occur in the context of an aplastic disorder. For example, Fanconi anemia is a congenital variation. Acquired disorders of blood cell (and, thus, thrombocyte) synthesis concern bone marrow lesions via radiation, chemicals, medicaments, infections (HIV) or antibodies. Also, bone marrow lesions are possible in the context of malignant infiltration at leukemia, carcinomas or lymphomas. Myeloproliferative diseases can likewise replace the bone marrow in the course of the respective disease.

Fanconi anemia blood smear

Image: “Peripheral blood smear and bone marrow aspirate. (A) Peripheral blood smear showing blast cells. (B) Bone marrow smear revealing a blast cell exhibiting an Auer rod.” by Openi. License: CC BY 2.0

Synthesis disorders can, however, also develop if the bone marrow is properly functioning. For example, maturation of the cells can be impaired, which occurs in states of vitamin deficiency. In this context, vitamin B12 or folic acid deficiencies are especially important.

Thrombocytopenia due to increased peripheral turnover

The bone marrow can compensate peripheral thrombocyte consumption well and for a long time. If this consumption exceeds the synthesis performance of the bone marrow, thrombocytopenia develops. The already relatively short lifespan of the thrombocytes amounts to roughly one week. In the event of increased consumption, the thrombocytes are partially consumed after a couple of hours. The turnover is enhanced to the fivefold. These numbers illustrate the capability of the bone marrow.

For the sake of a better overview (and for internalization) the peripheral consumption can be further divided:

Immune thrombocytopenia
Many mechanisms cause the occurrence of autoantibodies against thrombocytes. If thrombocytopenia is observed after a previous infection, an acute post-infectious immune thrombocytopenia (ITP) is probably present. If often affects children after gastrointestinal or respiratory viral infections. Mostly, the disease is self-limiting. In these cases, aspirin must not be given! If spontaneous healing up does not occur, glucocorticoids can be administered. Thrombocyte concentrations only become necessary in the event of life threatening bleedings.

Besides the acute form, there also is a chronic variation: the chronic immune thrombocytopenic purpura (= Werlhof’s disease). Hereby, autoantibodies are produced in the spleen. The disease is often associated with a Helicobacter pylori-gastritis. Therapeutically, immune suppressive therapy is initiated (glucocorticoids, immune globulins or rituximab) besides the H. pylori eradication and temporizing behavior. The last-resort measure is the indication for splenectomy.

Skeletal formula of Argatroban

Image: “Skeletal formula of argatroban, a direct thrombin inhibitor as an alternative to heparin in HIT” by Fvasconcellos. License: Public Domain

Also, medicaments can provoke antibody production. If thrombocytopenia manifests under the intake of medicaments, all medicaments should primarily be discontinued. A special and remarkable variation is heparin-induced thrombocytopenia (HIT), during which antibodies are produced against the heparin/platelet factor-4-complex due to heparins. This syndrome is potentially life threatening. Therapy has to be stopped and changed immediately.

Autoantibodies can also be produced in the context of several underlying diseases, e.g. at systemic Lupus erythematodes and rheumatoid arthritis, at HIV-infection, via malignant lymphoma or at the HELLP syndrome. It is also important to consider allo-antibody-induced thrombocytopenia after transfusions.

Thrombocytopenia due to enhanced thrombin activity
Enhanced thrombin activity can be observed at disseminated intravascular coagulation (DIC) and at malignant and infectious processes.

Thrombocytopenia of mechanical genesis
Implanted artificial cardiac valves can mechanically damage the thrombocytes and, thus, alter the blood count. Also, extracorporeal exchange measures like dialysis or heart-lung-machines show a similar effect.

Thrombocytopenia of other causes
Thrombocytopenia often occurs in the context of splenomegaly. On the one hand, the spleen makes for pooling of the thrombocytes and simultaneously causes increased degradation. Compared to the synthesis disorders in the bone marrow, also all cell lines are mostly affected. Thrombotic microangiopathy or the hemolytic-uremic syndrome also lead to thrombocytopenia via the development of thrombi rich in thrombocytes with microangiopathy.



Image: “Blood smear of an EDTA sample showing activated lymphocytes and platelet aggregates” by Openi. License: CC BY 2.0

Blood taking technique can lead to false conclusions and make you suspect thrombocytopenia. Due to EDTA-agglutinins or cold agglutinins, very low thrombocyte counts can be written on the laboratory printout, without your patient showing clinical symptoms. Before you inform the chief resident or even give your patient a well-meant therapy, you should at first take another, sovereign blood sample and send it in; this time, preferably in citrate-blood.

Signs and Symptoms of Thrombocytopenia

Clinical presentation of thrombocytopenia


Image: “Purpura spots” by Hektor. License: CC BY-SA 3.0

Clinically, thrombocytopenia becomes relevant at values of under 80,000/µl since increased bleeding tendency has to be assumed at this level, as long as no functional disorder of the thrombocytes (thrombocytopathy) is present. The classic characteristic of thrombocytic bleedings are petechiae, which develop at thrombocyte counts of under < 50,000/µl. Depending on the underlying disease, further symptoms can be manifold and heterogeneous. You have to ask all the more exactly for the possible clinical manifestation of a suspected underlying disease in the event of detected thrombocytopenia.

Diagnosis of Thrombocytopenia

Thrombocytopenia needs extensive anamnesis

The diagnosis of thrombocytopenia is made if less than 140,000 thrombocytes per µl blood are present. Diagnostically, you have to perform extensive and targeted anamnesis, which narrows your differential diagnostics down. Additionally, you should proceed with diagnostics concerning a possibly existing underlying disease progressively. In case of blood diseases, all cell lines absolutely have to be determined and evaluated!

Bone marrow analysis in thrombocytopenia

Bone marrow biopsy increased megakaryocytes

Image: “Bone marrow biopsy in essential thrombocytosis showing increased megakaryocytes.” by Openi. License: CC BY 2.0

Diagnostics can include bone marrow analysis. If the megakaryocyte count is decreased, a synthesis disorder is present. In the event of an increased megakaryocyte count, a maturation or turnover disorder exists. Of course, bone marrow analysis makes direct conclusions to primary or secondary bone marrow malignomas possible.

Therapy of Thrombocytopenia

How do I treat thrombocytopenia?

Therapy follows the extent and the kind of thrombocytopenia. A pre-existing disease should be treated if possible. Causing medicament intake should be discontinued.

Symptomatically, thrombocytopenia is balanced with transfusions of thrombocyte concentrations. In advance to different interventional or surgical measures, the thrombocyte count should be raised to certain values to minimize the risk of severe blood loss. As a benchmark, you can memorize a target thrombocyte count of > 50,000/µl. Thrombocyte concentrations are either gained from freshly taken whole-blood units or via mechanical thrombocyte apheresis.

If no significant increase in thrombocyte count occurs after the administration of thrombocyte concentrations, you should clarify the cause for this.  The following causes should be considered:

  • Splenomegaly, fever, sepsis, DIC, infections, or bleedings: The new thrombocytes are directly consumed.
  • Immunological factors: Antibodies eliminate the new thrombocytes.

More Information about Thrombocytopathies

Thrombocytic bleeding behavior can also occur at normal thrombocyte values. In such a case, one should consider thrombocyte function disorders, which can occur in the context of different inherited receptor of metabolic diseases or simply due to therapy with antiplatelet drugs.

Popular Exam Questions regarding Thrombocytopenia

1. For a long time, your patient has Werlhof’s disease (chronic immune thrombocytopenic purpura), which you can only insufficiently treat with glucocorticoids. You discuss splenectomy. Which is true concerning this procedure?

  1. Previous to splenectomy, you should perform immunizing therapy against sexually transmitted diseases on the patient.
  2. Due to the young age and the healthy constitution, there is no increased propensity for infections after splenectomy.
  3. Signs of extramedullary hematopoiesis can be found in the surgical preparation.
  4. The spleen should be removed since it is probably the production location of the autoantibodies. Splenectomy is no appropriate form of therapy at Werlhof’s disease.

2. You work in your own pediatric practice. For several weeks, you attend an elementary school child, which had multiple petechiae in the context of an infection. You diagnose acute post-infectious autoimmune thrombocytopenia. What is correct?

  1. There is an immediate call for action to avoid the risk of bleedings.
  2. Your only option is waiting.
  3. The intravenous application of immune globulins is the first-resort therapy.
  4. The application of thrombocyte concentrations is the first-resort therapy.
  5. The application of glucocorticoids is the first-resort therapy.

3. You work a night shift. The laboratory calls and announces a distinct thrombocytopenia in your recently admitted patient. You reconsider the physical examination and cannot recall to have seen petechiae or hematomas. Which cause you can most likely exclude?

  1. Asplenia
  2. Stage B HIV infection
  3. Werlhof’s disease
  4. Systemic Lupus erythematodes
  5. Acute leukemia

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