Immune Thrombocytopenic Purpura

Hematology

Clinicals - History

Fact Explanation
Introduction Immune thrombocytopenic purpura is a condition associated with autoantibody production(IgG) against one or more glycoproteins(eg; GPIIb, GPIIIa, Ib complex) in platelet membrane causing premature platelet destruction leading to thrombocytopenia. There is an autoantibody specificity against this glycoproteins. This premature platelet destruction is done by monocyte- macrophage system.
In children this condition usually occur following a viral infection as a sudden onset bruising or with spontaneous mucosal bleeding.
In adults this has an insidious onset, common among females and will remain as a chronic relapsing and remitting disease.
Introduction
Immune thrombocytopenic purpura is a condition associated with autoantibody production(IgG) against one or more glycoproteins(eg; GPIIb, GPIIIa, Ib complex) in platelet membrane causing premature platelet destruction leading to thrombocytopenia. There is an autoantibody specificity against this glycoproteins. This premature platelet destruction is done by monocyte- macrophage system.
In children this condition usually occur following a viral infection as a sudden onset bruising or with spontaneous mucosal bleeding.
In adults this has an insidious onset, common among females and will remain as a chronic relapsing and remitting disease.
History of suggestive of increased bleeding tendency Patient will present with multiple bruises, groups of pinpoint-sized dots on the skin and some times with bleeding from mucus membranes like gum bleeding, nasal bleeding. History of suggestive of increased bleeding tendency
Patient will present with multiple bruises, groups of pinpoint-sized dots on the skin and some times with bleeding from mucus membranes like gum bleeding, nasal bleeding.
Neurologic manifestations Neurologic manifestations such as alteration in mental status like confusion and drowsiness, seizures, muscle paralysis, paresthesias, blurred vision and headache will develop following intracranial haemorrhages. This is rare and only occur in severe cases with the platelet count less than 10 × 109/L . Neurologic manifestations
Neurologic manifestations such as alteration in mental status like confusion and drowsiness, seizures, muscle paralysis, paresthesias, blurred vision and headache will develop following intracranial haemorrhages. This is rare and only occur in severe cases with the platelet count less than 10 × 109/L .
Easy fatigue, shortness of breath, tiredness Theae features suggestive of anaemia may be present in patients with bleeding. Bleeding causes iron deficiency anaemia. Easy fatigue, shortness of breath, tiredness
Theae features suggestive of anaemia may be present in patients with bleeding. Bleeding causes iron deficiency anaemia.
History suggestive of a recent viral infection few weeks back Immune Thrombocytopenic Purpura can present following a viral infection like upper respiratory tract infection( cough, earache, throat ache, nasal congestion) and diarrhoeal illness. This is a common presentation in paediatric population.
Some viral infections like dengue, epstein-Barr virus, varicella virus, cytomegalo virus, rubella virus and hepatitis virus also can cause induce thrombocytopenia.
History suggestive of a recent viral infection few weeks back
Immune Thrombocytopenic Purpura can present following a viral infection like upper respiratory tract infection( cough, earache, throat ache, nasal congestion) and diarrhoeal illness. This is a common presentation in paediatric population.
Some viral infections like dengue, epstein-Barr virus, varicella virus, cytomegalo virus, rubella virus and hepatitis virus also can cause induce thrombocytopenia.
Past medical history If the patient is a diagnosed patient with Immune Thrombocytopenic Purpura full history about previous episodes need to be taken like exacerbating factors, severity of previous episodes and treatments given.
past medical history of some systemic illnessess like SLE, antiphospholipid syndrome, myelodysplastic syndrome, acute and chronic Leukemia(adults),Hodgkin’s disease, non-Hodgkin’s lymphomas and large granulocytic leukemia and Primary immunodeficiency conditions in children.
Past medical history
If the patient is a diagnosed patient with Immune Thrombocytopenic Purpura full history about previous episodes need to be taken like exacerbating factors, severity of previous episodes and treatments given.
past medical history of some systemic illnessess like SLE, antiphospholipid syndrome, myelodysplastic syndrome, acute and chronic Leukemia(adults),Hodgkin’s disease, non-Hodgkin’s lymphomas and large granulocytic leukemia and Primary immunodeficiency conditions in children.
Immunization history Transient thrombocytopenia is some times associated with vaccination( eg; live attenuated vaccines like MMR, and influenza vaccine). Immunization history
Transient thrombocytopenia is some times associated with vaccination( eg; live attenuated vaccines like MMR, and influenza vaccine).
Drug history Some drugs like chemotherapy causes generalzed myelosuppression causing platelet reduced platelet production and drugs like thiazide diuretics, ethanol and tolbutamide causes isolated thrombocytopenia by selective suppression of megakaryocyte production.some antineoplastic drus are leads to premature platelet dystruction ultimately causing thrombocytopenia. Drug history
Some drugs like chemotherapy causes generalzed myelosuppression causing platelet reduced platelet production and drugs like thiazide diuretics, ethanol and tolbutamide causes isolated thrombocytopenia by selective suppression of megakaryocyte production.some antineoplastic drus are leads to premature platelet dystruction ultimately causing thrombocytopenia.

Clinicals - Examination

Fact Explanation
Signs of increase bleeding tendency There will be multiple purpura/ ecchymotic patches and groups of petechiae and evidence of gum/ nasal bleeding or bleeding from other mucus membranes( gastrointestinal bleeding will present as either malena/ haematochaezia or haemoptysis, genitourinary bleeding will give haematuria). If patient develop retroperitoneal/ intraperitoneal bleeding there will be signs of acute abdomen (tender abdomen, garding, rigidity and psoas sign). If there is muscle bleeding muscle tenderness will be present. Usually bleeding manifestations are rare with this condition other than skin manifestations and patient will be other wise healthy in physical examination if there are no associated complications.
Rare but serious intracranial haemorrhages can also be a presentation and will discuss separately.
Signs of increase bleeding tendency
There will be multiple purpura/ ecchymotic patches and groups of petechiae and evidence of gum/ nasal bleeding or bleeding from other mucus membranes( gastrointestinal bleeding will present as either malena/ haematochaezia or haemoptysis, genitourinary bleeding will give haematuria). If patient develop retroperitoneal/ intraperitoneal bleeding there will be signs of acute abdomen (tender abdomen, garding, rigidity and psoas sign). If there is muscle bleeding muscle tenderness will be present. Usually bleeding manifestations are rare with this condition other than skin manifestations and patient will be other wise healthy in physical examination if there are no associated complications.
Rare but serious intracranial haemorrhages can also be a presentation and will discuss separately.
Pallor This is rare and can associated secondary to excessive bleeding following thrombocytopenia. Also useful in ruling out other primary causes like chronic systemic illnessess (SLE, antiphospholipid syndrome, myelodyasplastic syndrome) leading to thrombocytopenia. Pallor
This is rare and can associated secondary to excessive bleeding following thrombocytopenia. Also useful in ruling out other primary causes like chronic systemic illnessess (SLE, antiphospholipid syndrome, myelodyasplastic syndrome) leading to thrombocytopenia.
Neurologic examination Neurologic examination reveals alteration in mental status( confusion/ drowsiness), development of seizures, hemiplegia, paresthesias, visual disturbance following an intracranial haemorrhage. Recent asymmetrical findings in neurological examination will suggest intra creanial haemorrhages in patients with ITP. Neurologic examination
Neurologic examination reveals alteration in mental status( confusion/ drowsiness), development of seizures, hemiplegia, paresthesias, visual disturbance following an intracranial haemorrhage. Recent asymmetrical findings in neurological examination will suggest intra creanial haemorrhages in patients with ITP.
Fundoscopic examination This will reveals the presence of any retinal haemorrhages and vitreous haemorrhages. If the patient is having increased intracranial pressure following intra cranial haemorrhages there will be papilloedema . Fundoscopic examination
This will reveals the presence of any retinal haemorrhages and vitreous haemorrhages. If the patient is having increased intracranial pressure following intra cranial haemorrhages there will be papilloedema .
Splenomegaly Splenomegaly is not a typical presentation in this condition but can occur following increased platelet destruction. But if splenomegaly is present, need to exclude other causes which are associated with splenomegaly like thrombotic thrombocytopenia purpura. Splenomegaly
Splenomegaly is not a typical presentation in this condition but can occur following increased platelet destruction. But if splenomegaly is present, need to exclude other causes which are associated with splenomegaly like thrombotic thrombocytopenia purpura.
Fever, ill health, cough, skin rash, lympadenopathy suggestive of recent viral infection Some viral infections like dengue, epstein-Barr virus, varicella virus, cytomegalo virus, rubella virus and hepatitis virus also can cause induce thrombocytopenia. Fever, ill health, cough, skin rash, lympadenopathy suggestive of recent viral infection
Some viral infections like dengue, epstein-Barr virus, varicella virus, cytomegalo virus, rubella virus and hepatitis virus also can cause induce thrombocytopenia.
Skin rashes, oral ulcers, lymphadenopathy, joint inflammation, low grade fever, oral trush, hepatospenomegaly and anaemia like features suggestive of sysrtemic illnessess. As systemic illnessess like SLE, antiphospholipid syndrome, myelodysplastic syndrome, acute and chronic Leukemia(adults),Hodgkin’s disease, non-Hodgkin’s lymphomas and large granulocytic leukemia and Primary immunodeficiency conditions in children can induce thrombocytopenia these conditions need to be excluded.
7) Immunization history Transient thrombocytopenia is some times associated with vaccination( eg; live attenuated vaccines like MMR, and influenza vaccine).
8) Drug history Some drugs like chemotherapy causes generalzed myelosuppression causing platelet reduced platelet production and drugs like thiazide diuretics, ethanol and tolbutamide causes isolated thrombocytopenia by selective suppression of megakaryocyte production.some antineoplastic drus are leads to premature platelet dystructio
Skin rashes, oral ulcers, lymphadenopathy, joint inflammation, low grade fever, oral trush, hepatospenomegaly and anaemia like features suggestive of sysrtemic illnessess.
As systemic illnessess like SLE, antiphospholipid syndrome, myelodysplastic syndrome, acute and chronic Leukemia(adults),Hodgkin’s disease, non-Hodgkin’s lymphomas and large granulocytic leukemia and Primary immunodeficiency conditions in children can induce thrombocytopenia these conditions need to be excluded.
7) Immunization history Transient thrombocytopenia is some times associated with vaccination( eg; live attenuated vaccines like MMR, and influenza vaccine).
8) Drug history Some drugs like chemotherapy causes generalzed myelosuppression causing platelet reduced platelet production and drugs like thiazide diuretics, ethanol and tolbutamide causes isolated thrombocytopenia by selective suppression of megakaryocyte production.some antineoplastic drus are leads to premature platelet dystructio
Hypertension and bradycardia. This combination will suggest the increased intracranial pressure. In here Increased intracranial pressure exceeds the mean arterial pressure and cerebral perfusion get diminished, which leads activation of sympathetic system which causes hypertension and tachycardia initially via alpha 1 receptors. Mean while the baroreceptors get stimulated and causes bradycardia via vagal stimulation. Hypertension and bradycardia.
This combination will suggest the increased intracranial pressure. In here Increased intracranial pressure exceeds the mean arterial pressure and cerebral perfusion get diminished, which leads activation of sympathetic system which causes hypertension and tachycardia initially via alpha 1 receptors. Mean while the baroreceptors get stimulated and causes bradycardia via vagal stimulation.

Investigations - Diagnosis

Fact Explanation
Full blood count Platelet count is normally in between 10-50x 109/L. Usually other cell counts are normal. But if there is any ongoing infection there will be increase in WBC count and if the excessive bleeding is present there will be low haemoglobin levels due to iron deficiency anaemia. Full blood count
Platelet count is normally in between 10-50x 109/L. Usually other cell counts are normal. But if there is any ongoing infection there will be increase in WBC count and if the excessive bleeding is present there will be low haemoglobin levels due to iron deficiency anaemia.
Peripheral blood film examination Reduced number of platelet count will be present. Morphology of red blood cells and WBC will be normal in the absent of other complications. Peripheral blood film examination
Reduced number of platelet count will be present. Morphology of red blood cells and WBC will be normal in the absent of other complications.
Bone marrow biopsy This will show normal or increased levels of megakaryocytes. This bone marrow biopsy should be done before starting steroid treatment as it can interfere with the morphology of platelets. This is useful in excluding other differential diagnosis like myelodysplastic syndrome as well. Bone marrow biopsy
This will show normal or increased levels of megakaryocytes. This bone marrow biopsy should be done before starting steroid treatment as it can interfere with the morphology of platelets. This is useful in excluding other differential diagnosis like myelodysplastic syndrome as well.
Tests for platelet antigen–specific antibodies, platelet-associated immunoglobulin and antiplatelet antibodies These tests are useful in assesing the presence of auto antibody levels in the body.Eg; antiglycoprotein GPIIb, IIIa or GPIb antibodies on platelet surface. Tests for platelet antigen–specific antibodies, platelet-associated immunoglobulin and antiplatelet antibodies
These tests are useful in assesing the presence of auto antibody levels in the body.Eg; antiglycoprotein GPIIb, IIIa or GPIb antibodies on platelet surface.
Antinuclear antibodies In a symptomatic chronic disease state, negativity of this will be useful in excluding other conditions and come to the diagnosis of chronic Immune Thrombocytopenic Purpura. Antinuclear antibodies
In a symptomatic chronic disease state, negativity of this will be useful in excluding other conditions and come to the diagnosis of chronic Immune Thrombocytopenic Purpura.
PT/INR, APTT As there is no clotting factor defect these tests are normal and helps in differentiating this bleeding tendency with other clotting disorders. PT/INR, APTT
As there is no clotting factor defect these tests are normal and helps in differentiating this bleeding tendency with other clotting disorders.
Computed tomography (CT) scanning and magnetic resonance imaging (MRI) CT scanning or MRI useful in the medical history or physical findings suggest serious internal bleeding. Computed tomography (CT) scanning and magnetic resonance imaging (MRI)
CT scanning or MRI useful in the medical history or physical findings suggest serious internal bleeding.

Investigations - Management

Fact Explanation
Full Blood Count This is useful in follow up to see the level of thrombocytopenia. Full Blood Count
This is useful in follow up to see the level of thrombocytopenia.
Clotting profile with prothrombin time and activated partial thromboplastin time This is useful in excluding any associated clotting factor deficiency. Clotting profile with prothrombin time and activated partial thromboplastin time
This is useful in excluding any associated clotting factor deficiency.
CT scanning /MRI CT scanning or MRI will useful in follow up in the medical history or physical findings suggest serious internal bleeding. CT scanning /MRI
CT scanning or MRI will useful in follow up in the medical history or physical findings suggest serious internal bleeding.
Full Blood Count Assess the degree of thrombocytopenia will helpful in deciding the patients present condition and also helpful as a test of assessing the fitness of patients awaiting for splenectomy. Full Blood Count
Assess the degree of thrombocytopenia will helpful in deciding the patients present condition and also helpful as a test of assessing the fitness of patients awaiting for splenectomy.
Fasting blood sugar This is being done as a test of assessing the fitness of patients awaiting for splenectomy, to see the blood sugar control. Fasting blood sugar
This is being done as a test of assessing the fitness of patients awaiting for splenectomy, to see the blood sugar control.
Renal function test including serum electrolytes, blood urea and serum creatinine These are tests used to assess the basic fitness of patients awaiting for splenectomy, to see the renal function of the patient. Renal function test including serum electrolytes, blood urea and serum creatinine
These are tests used to assess the basic fitness of patients awaiting for splenectomy, to see the renal function of the patient.
Clotting profile including PT/INR, APTT This use to assess the clotting status of the patient and usually done as a test of assessing the fitness of patients awaiting for splenectomy. Clotting profile including PT/INR, APTT
This use to assess the clotting status of the patient and usually done as a test of assessing the fitness of patients awaiting for splenectomy.
ECG This is useful in assessing cardiovascular fitness and also helpful in diagnosis as the ECG leads(which induced a suction over the skin) can induce petechiae following bleeding from capillaries. ECG
This is useful in assessing cardiovascular fitness and also helpful in diagnosis as the ECG leads(which induced a suction over the skin) can induce petechiae following bleeding from capillaries.
Computed tomography (CT) scanning and magnetic resonance imaging (MRI) CT scanning or MRI useful in the medical history or physical findings suggest serious internal bleeding. Computed tomography (CT) scanning and magnetic resonance imaging (MRI)
CT scanning or MRI useful in the medical history or physical findings suggest serious internal bleeding.
ESR, CRP and disease specific serological antigens No specific test for screening the disease but as these patients are at risk of getting infections screening for infections can be done with ESR, CRP and disease specific serological antigens. ESR, CRP and disease specific serological antigens
No specific test for screening the disease but as these patients are at risk of getting infections screening for infections can be done with ESR, CRP and disease specific serological antigens.
Enzyme immunoassay for HIV There is a relationship in between thrombocytopenia and HIv infection. The exact mechanism is not identified but there are suggestions about the pathophysiology. One is the direct HIV infection of the megakaryotypes leading to dystruction of cells. Another theory is HIV infection leads to production of abnormal megakaryocytes causing abnormal platelets. Also other theory says cross reaction of HIV antibodies with platelets leads to premature platelet destruction causing thrombocytopenia.In a blood picture of a HIV patient there are apoptic megakaryocytes and clustered megakaryocytes. Enzyme immunoassay for HIV
There is a relationship in between thrombocytopenia and HIv infection. The exact mechanism is not identified but there are suggestions about the pathophysiology. One is the direct HIV infection of the megakaryotypes leading to dystruction of cells. Another theory is HIV infection leads to production of abnormal megakaryocytes causing abnormal platelets. Also other theory says cross reaction of HIV antibodies with platelets leads to premature platelet destruction causing thrombocytopenia.In a blood picture of a HIV patient there are apoptic megakaryocytes and clustered megakaryocytes.

Management - Supportive

Fact Explanation
Health education Patient/ care givers should be aware about the condition, symptoms, treatment options complications and prognosis. Health education
Patient/ care givers should be aware about the condition, symptoms, treatment options complications and prognosis.
Post splenectomy care Patients are at risk of getting infections from encapsulated organisms. Vaccination should be done( against Haemophilus influenzae type b vaccine, polyvalent Streptococcus pneumoniae vaccine and meningococcal polysaccharide vaccine and annual influenza vaccine). Prevention, early diagnosis and early tratment for infections is also very important. Post splenectomy care
Patients are at risk of getting infections from encapsulated organisms. Vaccination should be done( against Haemophilus influenzae type b vaccine, polyvalent Streptococcus pneumoniae vaccine and meningococcal polysaccharide vaccine and annual influenza vaccine). Prevention, early diagnosis and early tratment for infections is also very important.
Antibiotic therapy As these patients are at risk of getting infections, if a patient present with fever they should be treated with IV antibiotics until excluding a bacterial infection excluded. Antibiotic therapy
As these patients are at risk of getting infections, if a patient present with fever they should be treated with IV antibiotics until excluding a bacterial infection excluded.

Management - Specific

Fact Explanation
Observation If the patient is asymptomatic or present with mild bleeding observation alone is enough regardless of the platelet count of the patient. Observation
If the patient is asymptomatic or present with mild bleeding observation alone is enough regardless of the platelet count of the patient.
corticosteroids like oral prednisone, intravenous [IV] methylprednisolone or high-dose dexamethasone This is the first line treatment in acute Immune Thrombocytopenic Purpura. Corticosteroids are useful in reducing the platelet destruction by auto antibodies by inducing immunosuppressive state. Also it is useful in repairing the endothelial damage and by that it maintain haemostasis and minimize bleeding. corticosteroids like oral prednisone, intravenous [IV] methylprednisolone or high-dose dexamethasone
This is the first line treatment in acute Immune Thrombocytopenic Purpura. Corticosteroids are useful in reducing the platelet destruction by auto antibodies by inducing immunosuppressive state. Also it is useful in repairing the endothelial damage and by that it maintain haemostasis and minimize bleeding.
IV immunoglobulin (IVIG) This is the second line medication following corticosteroid therapy. High dose of IV immunoglobulin helps in increasing platelet count rapidly by blocking receptors on macrophages or modifying autoantibody production. This is useful in life threatening haemorrhages, steroid refractory disease, pregnancy and before surgical procedures. IV immunoglobulin (IVIG)
This is the second line medication following corticosteroid therapy. High dose of IV immunoglobulin helps in increasing platelet count rapidly by blocking receptors on macrophages or modifying autoantibody production. This is useful in life threatening haemorrhages, steroid refractory disease, pregnancy and before surgical procedures.
Immunosuppressive therapy( eg; cyclophosphamide, azothioprine) Theses drugs are use either individually or as combinations in patients who are not respond to other treatments. Immunosuppressive therapy( eg; cyclophosphamide, azothioprine)
Theses drugs are use either individually or as combinations in patients who are not respond to other treatments.
Monoclonal antibody therapy Rituximab is also used in Immune Thrombocytopenic Purpura patients. This is also proven to be benefited in treatment. Monoclonal antibody therapy
Rituximab is also used in Immune Thrombocytopenic Purpura patients. This is also proven to be benefited in treatment.
Androgens( eg; Danazol) Androgens are known to increase platelet count by reducing the destruction of immunoglobulin-coated platelets and also by decreasing the auto antibody production. In here often necessary to combine with an immunosuppressive medication. Androgens( eg; Danazol)
Androgens are known to increase platelet count by reducing the destruction of immunoglobulin-coated platelets and also by decreasing the auto antibody production. In here often necessary to combine with an immunosuppressive medication.
Thrombopoietin-Receptor Agonists This is a newer treatment option which is more important as it directly stimulate the platelet production via stimulating bone marrows. Thrombopoietin-Receptor Agonists
This is a newer treatment option which is more important as it directly stimulate the platelet production via stimulating bone marrows.
Platelet transfusion This is useful in acute life threatening conditions but the benefit will last only for few hours. Platelet transfusion
This is useful in acute life threatening conditions but the benefit will last only for few hours.
Splenectomy This is recommended in symptomatic patients with platelet count less than 30x 109/L, after 3 months of steroid therapy. This is more effective in acute conditions but less effective in chronic status. Splenectomy
This is recommended in symptomatic patients with platelet count less than 30x 109/L, after 3 months of steroid therapy. This is more effective in acute conditions but less effective in chronic status.
Stem cell transplantation This is identified as a curable treatment option in severe cases. Stem cell transplantation
This is identified as a curable treatment option in severe cases.
ITP management in pregnancy by monitoring and medical treatments. FBC should be done every 2-4 weekly to assess the level of thrombocytopenia.
If patient is asymptomatic and platelet count is more than 50x 109/L , no treatment will be needed other than close monitoring.
If the patient is having bleeding or platelet count is less than 50x 109/L oral steroid treatment will be useful.
If patients condition is not improving with the steroids IV immunoglobuline need to be considered.
Splenectomy is rarely indicated in pregnancy.
Platelet transfusion will be useful where rapid correction is needed.
close monitoring should be done as patient is at risk of antenatal and intrapartum bleeding
During labour foetal scalp electrodes, foetal blood sampling, ventous delivery and rotational forceps delivery need to be avoided.
Cord blood should be tested for platelet count( as IgG antiplatlet antibodies can cross the placenta and leads to foetal thrombocytopenia .
ITP management in pregnancy by monitoring and medical treatments.
FBC should be done every 2-4 weekly to assess the level of thrombocytopenia.
If patient is asymptomatic and platelet count is more than 50x 109/L , no treatment will be needed other than close monitoring.
If the patient is having bleeding or platelet count is less than 50x 109/L oral steroid treatment will be useful.
If patients condition is not improving with the steroids IV immunoglobuline need to be considered.
Splenectomy is rarely indicated in pregnancy.
Platelet transfusion will be useful where rapid correction is needed.
close monitoring should be done as patient is at risk of antenatal and intrapartum bleeding
During labour foetal scalp electrodes, foetal blood sampling, ventous delivery and rotational forceps delivery need to be avoided.
Cord blood should be tested for platelet count( as IgG antiplatlet antibodies can cross the placenta and leads to foetal thrombocytopenia .

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