Answer To Recent Case

Dear Bloggers

Here are the answers to the recent case.

Question 1: Taking into account the history and examination what other feature from the CBC do you think is abnormal in this case?

The other abnormal feature is the platelet count. In fact, she had only 3,000 per microlitre of platelets hence, Severe thrombocytopaenia. Her WBC count was normal, as was her haemoglobin and other coagulation studies.

Question 2: Why are her legs most affected and what is likely to be the likely diagnosis ?

Her legs were most affected because of the effect of gravity and venous pooling. The blood being under a column of pressure and with low platelets resulted in severe petechial haemorrhage.

In view of the recent infection, and no other sinister findings being found on examination such as lymphadenopathy, the suspected diagnosis was a viral induced thrombocytopaenia. ITP was also considered strongly in view of the patient's presentation, her female gender, a normal sized spleen and absence of other symptoms.

Of course, malignancy e.g. MDS, leukaemia, other autoimmune diseases e.g. SLE, were considered, but in view of an otherwise normal blood differential and no other features consistent with these pathologies, they were not really considered to be likely as the cause.

Question 3: Why might the BUN be raised?

The BUN may have been raised because of asymptomatic gastric haemorrhage.

Question 4: Would you admit this patient into hospital even though she feels well or would you let her go home?

This patient is high risk for parenchymal haemorrhage. Initially, low platelets results in cutaneous petechiae. If the platelet count worsens, then mucosal bleeding occurs. At this point, one should be highly suspicious of potential severe bleeding ensuing e.g. intracranial haemorrhage, GI bleeding.

Hence, the patient should not be sent home and should be admitted to hospital for investigation and prompt treatment.

Question 5: What other tests would you like to perform?

• The patient should have viral titres taken e.g. Adenovirus, Parvo Virus, Hep C, CMV, EBV, Mumps, Rubella Autoimmune profile e.g. Anti-DS DNA, ANA Abs for SLE
• Blood smear to look for abnormal cell morphology
• Anti-platelet antibodies (if available)
• Bone Marrow Examination-- essential to aid in the diagnosis
• Ultrasound of the abdomen to look for splenomegaly
• Ultrasound of the knee to look for haemarthrosis-- aspiration is not safe with profoundly low platelet counts.
• Rectal examination for occult bleeding (easy to do and often avoided!!)
  
• Gastroscopy and colonoscopy
  
• Treatment here would be to transfuse platelets and treat the underlying cause (if known)

The bone marrow examination revealed: increased numbers of megakaryocytes of normal morphology. There was also a slight increase in the erythroid precursors.

The serology revealed: a normal panel autoimmune profile e.g. normal levels of ANA.

Her viral serology showed past infection with CMV and EBV and Parvovirus and HCV were negative. Other viral serology was unfortunately no performed.

Abdominal ultrasound revealed a normal spleen.

Anti-platelet antibodies were positive with a level of 75 (normal <5).

Hence, in view of the clinical history, physical examination, the bone marrow examination and positive anti-platelet antibodies, it was considered that the diagnosis was:

Immune Thrombocytopaenic Purpura.

She received prednisolone at a dose of 1mg/kg/day -- 50mg in total, and her platelet count increased to 30,000 within 3 days with no new bleeding problems. However, despite high dose steroids, the platelet count did not increase much beyond this level thereby prompting the use of other treatment modalities (see description and treatment of ITP below)

Here is a most excellent response from Professor Masami Matsumura of Kanazawa University School of Medicine with his opinion on the case.

This is interesting case for approaching the diagnosis.

ID/CC: 50-year-old woman with a diffuse skin eruption

Problem list:

1. Episodes of URTI
2. Diffuse skin eruption, suspect petechiae
3. Oral mucosal bleeding
4. Left knee acute monoarthritis without trauma history
5. Oedema of both ankles
6. Mildly raised BUN (20.1)
7. Mild monocytosis
8. Mildly raised CRP

Assessment:

After episodes of URTI, she had left knee acute monoarthritis, diffuse skin eruption, and oral mucosal bleeding. These issues are consistent with Immune Thrombocytopenic Purpura (ITP). Another differential diagnosis is Henoch-Schonlein purpura. Acute polyarthritis is observed in this disorder. However, oral mucosal bleeding is not observed in Henoch-Schonlein purpura. Moreover, palpable purpura is characteristic of this disease. I think ITP is most likely in this case.

Another differential diagnoses are follows:

• Hematologic malignancies including CLL
• MDS
• SLE
• Viral infection including hepatitis C and HIV
• Evans’s syndrome

Question 1: Taking into account the history and examination what other feature from the CBC do you think is abnormal in this case?

This patient has mucosal bleeding. I think her platelet count is under 10,000/m(micro)L.

Question 2: Why are her legs most affected and what is likely to be the likely diagnosis ?

Her physical examination revealed acute monoarthritis in left knee. When we see acute monoarthritis, Gout, Pseudogout, Infectious arthritis, Bleeding, and Trauma (PIG TB is my mnemonics) must be differentiated. She denied trauma episode. Bleeding is most likely in this case.

Question 3: Why might the BUN be raised?

I suspect GI tract bleeding. GI tract bleeding can cause elevated BUN.

Question 4: Would you admit this patient into hospital even though she feels well or would you let her go home?

This patient must be admitted into hospital for close examination and treatment!!

Question 5: What other tests would you like to perform?

• Fundoscopy for examination retinal bleeding
• Peripheral blood cell morphology for detecting large platelets
• Coagulation studies including PT and APTT
• ANA, HCV antibody assay
• Abdominal echo for evaluate spleen size
• Bone marrow aspiration

An anonymous response was received as follows:

1.? Platelets>low; stool occult blood +
2. Henoch Schoelein, Behcet [pathergy from your History], Parvo 19, R/O DVT, anti-phospholipid syndrome
3. ^ BUN from GI bleed
4. In Japan, admit; in North America follow-up in clinic
5. Skin Bx, Fiber Colon/gastro filber if stool blood +; L knee OA

Immune Thrombocytopenic Purpura (ITP)

This is a bleeding disorder resulting from low platelets not associated with another systemic disease. For the diagnosis to be made, other disorders should be excluded through other tests. Autoantibodies are usually produced against the platelet resulting in the low platelet level. In children, a viral infection can also result in ITP.

The spleen is usually normal size except if there is co-existent viral infection.

The symptoms and signs are of petechiae and mucosal bleeding e.g. in the mouth, GI tract etc. Examination of the blood reveals an isolated reduction in platelets but an other normal morphology and differential of white cells and red levels.

Bone Marrow examination reveals normal or increased numbers of megakaryocytes with other bone marrow elements being normal. Other pathologies should be excluded as described above and HIV testing should be performed in those individuals considered to be at risk because this infection can appear in an identical way to ITP.

Treatment consists of corticosteroids e.g. Prednisolone 1mg/kg/day. In those patients who respond to treatment, the platelet count should increase to normal in 2-6 weeks. The steroid dose is then tapered accordingly. In patients who do not respond to treatment and in who have a high risk of haemorrhage, splenectomy is considered.

Other immunomodulatory treatments are sometimes used such as immune globulin transfusions, cyclophosphamide, azathioprine and the anti-CD20 antibody (Rituximab).


Many thanks for all those doctors who contributed to give their opinions on this case.

There will be more great cases coming....stay tuned!!! :-)