A 34 year old woman complains of feeling depressed for the past month. She is not complaining of any other symptoms and has no medical or drug history. On examination, there is no splenomegaly.
| Hb: | 133 g/L | |
| MCV: | 91 fL | (77-95 fL) |
| WCC: | 6.6 x 109 cells/L | |
| Platelets: | 58 x10x9/L |
Tests added based on platelet count:
| LDH: | 213 IU/L | (105 – 333 IU/L) |
| INR: | 1.1 | |
| APTT: | 31s | (30-50s) |
| B12: | 434 pg/ ml | (200 – 800 pg/mL) |
| Folate: | 7.6 ng/mL | (2 – 20 ng/mL) |
Blood film:
Thrombocytopenia confirmed. No fragmented cells. Normal red and white cell morphology. Slightly large platelets.
What is the most appropriate treatment for the likely diagnosis? (Answer at the bottom of this post)
A Platelet transfusion
B No treatment necessary
C Prednisolone
D Immunoglobulin
E Plasma exchange
Quick answer
What’s likely to be going on?
This patient is likely to have immune thrombocytopenia. This is because if isolated thrombocytopenia is picked up incidentally in an apparently asymptomatic patient with no relevant drug treatment and a normal blood film, the diagnosis is usually immune thrombocytopenia.
Why did we not have to give any treatment in this case?
“Treatment is rarely indicated in patients with platelet counts above 50 x 109/L in the absence of the following: bleeding due to platelet dysfunction or another hemostatic defect, trauma, surgery, clearly identified comorbidities for bleeding, mandated anticoagulation therapy, or in persons whose profession or lifestyle predisposes them to trauma.”
Full answer
We are presented with a 34 year old woman with thrombocytopenia. She has no symptoms that we can attribute directly to the low platelet count.
Why did the haemotologist say ‘thrombocytopenia confirmed’? Isn’t it obvious from the FBC?
On any sample reported as thromboycytopenia, one of the first things to do is a peripheral blood film. This not only helps with the differential, but is necessary to exclude clumping caused by EDTA antibodies or giant platelets failing to be counted by automated analysers. If there is clumping, a re-draw the blood in a citrate tube (the blue coagulation bottle) for a new FBC.
What are the causes of thrombocytopenia?
Once thrombocytopenia is confirmed, the causes can be split as shown:
Working through these options:
Decreased production
Bone marrow problem?
This could include myelodysplastic syndromes, leukemias, other malignancies, fibrosis and aplastic anemia. All of these are unlikely given the other two lines (red cells and white cells) are normal. The morphology on peripheral films shows no blast transformation or other indicators of malignancy.
Inadequate haematinics?
B12 and folate are within the reference range given and there are no symptoms or other lab results suggesting B12 deficiency. Bear in mind that a low-normal B12 in the usual reference range in UK labs does not rule out a B12 deficiency in a patient with symptoms of B12 deficiency. In Japan, the lower limit of a normal serum level for B12 is nearly twice that of the UK.
Increased consumption
Against bleeding:
- The patient is not complaining of any bleeding symptoms.
- The Hb is within the normal range.
Against DIC:
In addition to the lack of bleeding or thrombotic symptoms, the normal coagulation result makes DIC unlikely.
Mixed aetiology
Pregnancy?
Thrombocytopenia is not a presenting feature of pregnancy. Gestational thrombocytopenia is responsible for 75% of cases of thrombocytopenia in pregnancy, but typically occurs in the 3rd trimester. Important differentials in pregnancy include HELLP and DIC, both of which also tend to occur late in pregnancy.
Drug induced?
The patient is not on any medication.
Of note, heparin can cause a heparin-induced thrombocytopenia at 5-14 days after the first dose. The risk is 10x greater for unfractionated heparin as compared to LMWH. It’s worth noting that HIT is a prothrombotic state.
Alcohol is a very common common cause of thrombocytopenia, affecting 3 to 43 percent of nonacutely ill, well-nourished alcoholics and 14 to 81 percent of acutely ill, hospitalized alcoholics. You might expect a raised MCV and a relative neutropenia. You are going to need a sensitive alcohol history to explore this differential.
Infections?
Bacterial, viral and protozoan infections, both acute and chronic, can cause a thrombocytopenia. At the same time, a rise in platelets can be part of the acute inflammatory response. This means that during any acute infection the platelet count could be up, down or normal. This patient does not have any signs or symptoms of infection, and the WCC is normal.
Increased destruction
Against MAHA (microangiopathic hemolytic anemia)
- No fragmented cells
- Normal LDH
Against hypersplenism:
- No splenomegaly
- Normal red cell and white cell lines
ITP
Adult immune thrombocytopenia is usually a chronic, insidious condition which mostly affects women of childbearing age. Thrombocytopenia in ITP was traditionally blamed on increased platelet destruction mediated by autoantibodies and this is probably what they want you to know in MRCP questions. However, there is now increasing appreciation of impaired platelet production and T cell–mediated effects.
A presumptive diagnosis of ITP is made when the history, physical examination, complete blood count, and examination of the peripheral blood smear do not suggest other etiologies for the thrombocytopenia. There is no “gold standard” test that can reliably establish the diagnosis.
On examination, there may be slight splenomegaly. Massive splenomegaly would point to an alternative cause.
ITP can be primary or secondary. When secondary, it is usually associated with an autoimmune disorders or chronic infections such as Helicobacter pylori, hepatitis C virus or HIV. You would investigate each case for an underlying secondary cause depending on the individual’s risk factors and clinical presentation.
Managing ITP
Who to treat?
The decision to treat is based on the extent of any current bleeding, the risk of future bleeding, the risk of therapy and patient preference. In general, asymptomatic patients with no additional risk factors for bleeding with a platelet count above 50 do not usually need treatment.
How to treat
(OK. So when do we examine the bone marrow in thrombocytopenia?)
Bone marrow examination may be informative in patients older than 60 years of age, in those with systemic symptoms or abnormal signs, or in some cases in which splenectomy is considered.
The answer to the question above is B, no treatment needed.