The document discusses thrombocytopenia, characterized by a low platelet count, its causes, diagnosis, and treatment options. It details various types of thrombocytopenia, including idiopathic thrombocytopenic purpura (ITP), and outlines their clinical features, diagnostic procedures, and management strategies. Additionally, case scenarios illustrate potential presentations and diagnoses of thrombocytopenia in patients.

1. Thrombocytopenia
Usman Ali Shams
MLS M-Phil HaematoTechnology
University of Health Sciences
Lahore

2. Learning Objective
At the end of this session student will be able to understand the following
• thrombocytopenia
• different types and their causes of thrombocytopenia
• Review causes
• – Increased destruction
• – Decreased production
• Treatment – To transfuse or not?
• ITP & its types Acute and Chronic
• Case base scenario
• Kahoot play quiz

3. Thrombocytopenia
?

4. Thrombocytopenia
• Thrombocytopenia defines a subnormal number of platelets
in the circulating blood, usually below 100 × 109/L.
• A normal human platelet count ranges from 150,000 to 450,000 platelets
per microliter of blood.

5. Sign and Symptoms
The Symptoms of thrombocytopenia is not oftenly seen until the Platelets
level fall down below 50 x109/Ltr but upon falling down from the said level
clinical declaration occur.
A level less than 30 x109/Ltr can raise to possible symptoms like
Petechiae, menorrhagia, or spontaneous bruising.
A level less than 10 x109/Ltr can raise to the high-grade bleeding.
• Spontaneous Skin Purpura.
• Mucosal Hemorrhage.
• Prolonged Bleeding After Trauma.

8. Failure in Platelet Production

9. Increase Destruction Thrombocytopenia

10. • Increased sequestration i-e Hypersplenism
• Splenomegaly
Abnormal Distribution of platelets

11. Dilutional Loss
• Massive Transfusion

12. Different Causes of Thrombocytopenia
IL3 = interleukin3; GMCSF = granulocyte macrophage colony stimulating factor;
TPO = thrombopoietin; X = abnormal or absent

13. • We will only Discuss the Following
• Thrombocytopenia Due to Decrease Production of Thrombocytes i-e
1. Bone marrow Failure/suppression.
• Increased destruction of platelets i-e
1. Disseminated intravascular coagulation.
2. Increased splenic pooling
3. Massive transfusion syndrome
4. ITP
5. Drug Induced Thrombocytopenia.
6. Post-Transfusion Purpura.

14. Thrombocytopenia Due to Failure Production of
Platelets
• Most common cause of thrombocytopenia and occur due to Selective Bone
Marrow Suppression for producing Megakaryocytes Fragments.
• Bone marrow Failure can be occurred due to the Following Reasons.
• Cytotoxic Drugs & Radiotherapy (Direct effect the Bone marrow)
• Aplastic Anemias
• Leukemia
• Myelofibrosis
• Marrow Infiltration (e.g. Carcinoma, Lymphoma, Gaucher’s Disease)
• Megaloblastic Anemias
• HIV Infection (Direct effect the Megakaryocyte)

15. Thrombocytopenia Due to Failure Production of
Platelets CONT…….
• Bone Marrow Depression is rarely Congenital
• Occur by Mutation in c‐MPL thrombopoietin
receptor or of the RBM8A gene (RNA Binding
Motif Protein 8A) is a Protein Coding gene..
• The c-MPL gene provides instructions for making
the thrombopoietin receptor protein, which
promotes the growth and division (proliferation)
of cells.

16. Diagnosis of BM suppressed Thrombocytopenia
Diagnosis of these causes of thrombocytopenia is made from the
• Clinical history,
• Peripheral blood count,
• The blood film
• Bone marrow examination.

17. Thrombocytopenia Due to Increased
destruction/Usage of platelets
1. Disseminated intravascular coagulation:
• Disseminated intravascular coagulation (DIC) involves abnormal, excessive
generation of thrombin and fibrin in the circulating blood.
• During the process, increased platelet aggregation and coagulation factor
consumption occur.

18. 2. Increased spleenic pooling:
• Normally, the spleen stores one-third of the platelets that are produced by the
bone marrow and the remaining two-thirds of the platelets produced by the bone
marrow are in circulation.
• No platelets are stored in the bone marrow.
• If a condition causes the spleen to enlarge (splenomegaly), the spleen will
function abnormally, sequestering up to 90% of the total platelet mass in the
spleen.
• The result is a decrease in circulating platelets (thrombocytopenia).
• Conditions Include hepatic cirrhosis, Gaucher's disease(read comment), some
leukemias (like hairy cell leukemia).
Spleenic pooling Thrombocytopenia

20. 3. Massive Transfusion Syndrome:
• Platelets are unstable in blood Stored at Room Temperature i-e 24°C
• Platelets count rapidly fall stored for more than 24 hrs.
• Patient Transfused with Massive amount of stored blood such as 10 units in
24 hrs period will show abnormal clotting and thrombocytopenia.
• Patient with such condition can be Treated with Packed Platelets bag and
Fresh Frozen Plasma.(FFP)
Dilutional Thrombocytopenia

21. 4. Drug Induced Thrombocytopenia.
• Certain drugs can cause thrombocytopenia via immunological Response.
• Quinine (including that in tonic water), quinidine and heparin are
particularly common causes.
• Drug‐dependent antibodies against platelets may be demonstrated in the sera
of some patients.
• antibody–drug–protein complex is deposited on the platelet surface.
• If complement is attached and the sequence goes to completion, the platelet
may be lysed directly.
• Treatment: Can be Treated by Stop the administered Drug which is
suspected but in case of severe bleeding a patient must be given a platelet
concentration
Thrombocytopenia Due to Increased
destruction/Usage of platelets

22. Drug induced Thrombocytopenia

23. 6. Post-Transfusion Purpura.
• Rare but potentially lethal complication
• 7–10 days after transfusion of a platelet‐containing product, usually red cells.
• Caused by Allo-antibody in the recipient (resulting from previous transfusion or
pregnancy)
• which is usually directed against a platelet‐specific antigen HPA‐Ia (PIAI).
• Both the transfused and recipient platelets are destroyed by the immune complexes.
• Treatment It is usually self ‐ limiting but immunoglobulin or plasma exchange may be
needed
Thrombocytopenia Due to Increased
destruction/Usage of platelets

24. Any
Questions ?

25. Idiopathic Thrombocytopenic Purpura

26. Other names
• Idiopathic thrombocytopenic purpura (ITP),
• Immune thrombocytopenia,
• Primary immune thrombocytopenia,
• Primary immune thrombocytopenic purpura
• Autoimmune thrombocytopenic purpura
Idiopathic Thrombocytopenic Purpura (ITP)

27. • Idiopathic" means the cause is unknown.
• "Thrombocytopenia" means a decreased number of platelets in the blood.
• "Purpura" refers to the purple discoloring of the skin, as with a bruise.
Idiopathic Thrombocytopenic Purpura (ITP)

28. • Autoimmune destruction of platelets resulting thrombocytopenia
Or
• ITP is an autoimmune-mediated hematological disorder affecting
platelets. The immune system produces antibodies directed against
platelet antigens, resulting in platelet destruction and leading to an
increased risk of serious bleeding events
Idiopathic Thrombocytopenic Purpura (ITP)

30. Idiopathic Thrombocytopenic Purpura
• Acute thrombocytopenic purpura
• This is most common in children (2 to 6 years old).
• onset< 6months
• Spontaneous remissions are usual but in 5–10% of cases the disease becomes
chronic, lasting more than 6 months.
• Fortunately, morbidity and mortality in acute ITP is very low.
• The symptoms may follow a viral illness, such as chickenpox, EBV, H.pylori .

31. Acute ITP Diagnosis
• The diagnosis is one of exclusion. If the platelet count is over
30 x109/Ltr no treatment is necessary unless the bleeding is severe.
• Indeed many doctors do not treat even with platelet counts
< 10 x109/Ltr if there is no hemorrhage.
• Treatment is with steroids because they are immunosuppressant and/or intravenous
immunoglobulin(they inhibit macrophages activity), especially if there is significant
bleeding i-e Life threatening condition then go for platelet transfusion.

32. Idiopathic Thrombocytopenic Purpura
• Chronic thrombocytopenic purpura —
• Most common Disorder.
• The highest incidence has been considered to be in women aged 15–50 years.
• Chronic ITP implies disease that has been present for 12 months or more from
diagnosis
• The onset of the disorder can happen at any age, and the symptoms can last a
minimum of six months to several years.

33. Chronic ITP CONT.
• Usually idiopathic but may have seen associated with
• System Lupus Erythematosus (SLE)
• Human Immunodeficiency Virus (HIV) Infection,
• Viral Hepatitis,
• Chronic Lymphocytic Leukemia (CLL),
• Hodgkin Lymphoma Or Autoimmune Hemolytic Anemia.
Idiopathic Thrombocytopenic Purpura

34. Chronic ITP Pathogenesis
• Platelet auto antibodies, usually IgG, result in the premature removal of platelets from the
circulation by macrophages of the reticuloendothelial system, especially the spleen.
• In many cases, the antibody is directed against the glycoprotein (GP) IIb/IIIa or Ib
complex.
• The normal lifespan of a platelet is 10 days but in ITP this is reduced to a few hours.
• Total megakaryocyte mass and platelet turnover are increased in parallel to approximately
five times normal.

35. Platelets coated by antibodies are phagocytosed
by macrophages.
• Fc receptors of the splenic macrophages (M)
recognize antibody-sensitized platelets and
eliminate them from the circulation.
Pathogenesis

36. Clinical Feature for Chronic ITP
• Petechial hemorrhage,
• Easy Bruising
• In woman cause menorrhagia
• Mucosal bleeding (e.g. epistaxis or gum bleeding)
occurs in severe cases but intracranial hemorrhage is
rare.
• The main risk is of cerebral hemorrhage.

37. Characteristic Acute ITP Chronic ITP
Age at onset 2- 6 yr 20- 50 yr
Sex predilection None Female over male, 3: 1
Platelet count < 20,000/mcL 30,000- 80,000/mcL
Duration 2-6 weeks Months to years
Spontaneous remission 90% of patients Uncommon
Seasonal pattern
Higher incidence in winter and
spring
None
Prognosis Self limited Relapse
Antibody Auto-antibody against GpIIb/IIIa or Ib Auto-antibody against GpIIb/IIIa or Ib

38. Diagnosis of ITP
• The blood film shows reduced numbers of platelets, those present often being large.
• The bone marrow shows normal or increased numbers of megakaryocytes
• Sensitive tests are able to demonstrate specific anti‐glycoprotein GPIIb/IIIa or GPIb
antibodies on the platelet surface or in the serum in most patients.
• Platelet‐associated IgG assays are less specific. These tests are not usually used in
clinical practice.

39. Peripheral smear and bone marrow
examination of ITP

40. Chronic ITP Treatment
In general aim for treatment is to maintain the Platelet Count.
1. Corticosteroids 80%of patients remit on high‐ dose corticosteroid therapy. Prednisolone 1
mg/kg/day is the usual initial therapy in adults and the dosage is gradually reduced after 10–14
days. In poor responders the dosage is reduced more slowly but alternative immunosuppression or
splenectomy is considered.
2. High‐dose intravenous immunoglobulin therapy is able to produce a rapid rise in
platelet count in the majority of patients. A regimen of 400 mg/kg/day for 5 days or 1 g/kg/day for
2 days is used. The mechanism of action may be blockage of Fc receptors on macrophages or
modification of auto-antibody production.
3. Monoclonal antibody Rituximab (anti‐CD20) produces responses in approximately 50%,
which are often durable, and it is now usually tried before splenectomy.
4. Platelet transfusions Platelet concentrates are beneficial in patients with acute life‐threatening
bleeding, but their benefit will only last for a few hours.

41. References
• Post graduate haematology by Victor Hoffbrand 7th edition
• WinTrobe's Clinical Hematology 13th Edition
• William McKenzie Hematology.
• https://www.youtube.com/watch?v=iXsoxzx-uMw @medicosis_perfectionalis.

42. Any
Questions ?

43. Case Based Scenario 1
A 32 years female presented to emergency of a hospital with
random bruises and bleeding from gums on brushing teeth since one
week. Physical examination was normal. Hb 10.5 , MCV 70, TLC 7
and PLT 10 x 10˄9/Ltr. LFT were normal.
1. What are the likely peripheral blood film findings in this
case. What is the probable diagnosis?
ITP

44. A 32 weeks pregnant female presented with bruises and
ecchymosis spots on arms and trunk. Her peripheral blood
examination revealed TLC 8000, Hb 10.9 and PLT 7x10˄9/Ltr.
Also there were large megakaryocyte in bone marrow
examination.
Most probable Diagnosis????
Chronic ITP
Case Based Scenario 2

45. Feedback/Comments/suggestions?
OR
Portfolio(Reflection) to Dr. M Asif
Naveed