Thrombocytopenia? Differential diagnosis in three steps!

Step 1

Pseudothrombocytopenia
due to exclusionary EDTA-induced platelet aggregation.
Methods can be done by peripheral blood smear or repeat blood count (sodium citrate as an anticoagulant).

Another consideration is that healthy women may have mild to moderate thrombocytopenia (75-150x10^9/L) in pregnancy, and this transient reduction does not require extensive testing
.

Thrombotic thrombocytopenic purpura/haemolytic uremic syndrome (TTP/HUS) should be considered, as these conditions require special approaches to urgent treatment (e.
g.
, plasmapheresis).

A peripheral blood smear to look for schistocytes, plasma haptoglobin and LDH (to assess hemolysis), creatinine, and coagulation including
D dimer are recommended in all patients with thrombocytopenia.
TTP/HUS and DIC are characterized by hemolytic anemia of microangiopathies, schistocytes on peripheral smear, elevated LDH, and elevated
haptoglobin.
However, coagulation in TTP/HUS is usually normal, while DIC coagulation time is prolonged
.
Finally, if TTP/HUS is suspected, hematologist consultation is required
.

Drug-induced thrombocytopenia and hypersplenism should be considered
.
Patients with hypersplenism and cirrhosis are more likely to have thrombocytopenia
.
The drugs most commonly causing thrombocytopenia are antibiotics (including trimethoprim sulfamethoxazole compounds), cardiac drugs (eg, quinidine, procaine), thiazide diuretics, and antirheumatic drugs (such as gold salts and heparin).

Heparin-induced thrombocytopenia is potentially risky and requires immediate discontinuation of medications
, including heparin flush tubes.
Heparin-induced thrombocytopenia
can be diagnosed by in vitro testing for heparin-associated platelet antibodies.

After xenophobic microangiopathy, hemolytic anaemia, drug-induced thrombocytopenia, and hypersplenism, idiopathic thrombocytopenic purpura (ITP) is the leading cause
of isolated thrombocytopenia.
However, ITP is still an exclusionary diagnosis and cannot be diagnosed until other possible factors of exclusion, such as immune-mediated thrombocytopenia, including connective tissue disease, lymphoproliferation, and HIV infection
.
Therefore, we recommend testing for HIV, antinuclear antibodies, and monoclonal proteins
.
Conversely, we do not recommend platelet antibody testing or bone marrow biopsy
for ITP-associated isolated thrombocytopenia.

Rare, isolated thrombocytopenia such as hereditary thrombocytopenia may see large platelets on the peripheral blood smear (eg, May-Hegglin disease, gray platelet syndrome, Bernard-Soulier syndrome, and X-related Wiskott-Aldrich syndrome), spinal dysplasia syndrome (rarely manifested as thrombocytopenia alone), cytogenic thrombocytopenia (bone marrow biopsy is required) on the peripheral blood smear, and post-transfusion purpura (a rare complication of blood transfusion).

Post-transfusion purpura
should be considered in patients with recent (1 to 2 weeks) transfusions.
All of these possible conditions should be treated with a haematologist consultation
.