​Kembara Xtra - Medicine - Immune Thrombocytopenia

​Kembara Xtra - Medicine - Immune Thrombocytopenia 
ITP is a disorder marked by immunologic destruction of healthy platelets and/or defective thrombopoiesis in response to an unidentified stimuli.
Once all other causes of thrombocytopenia have been ruled out, it is defined as a platelet count of 100 109/L or more.

Nomenclature for ITP:
- Newly diagnosed (3 months), persistent (between 3 and 12 months), and chronic (more than 12 months)
- When it manifests alone, it is primary; when it is accompanied by other disorders, it is secondary.

ITP is a disorder that commonly develops in children after a viral infection. Within a week of onset, >80% of patients experience spontaneous remission within two months.
● ITP in adults is frequently a chronic condition, and spontaneous remission is uncommon.
Idiopathic thrombocytopenic purpura, immune thrombocytopenic purpura, and Werlhof illness are all possible synonyms.

Epidemiology 
Peak age for pediatric ITP is 2 to 4 years, but chronic ITP occurs beyond age 50, with incidence being 2 times greater in people over 60 than under 60. Predominant gender for pediatric ITP is male:female, while chronic ITP is female:female (1.2 to 1.7:1)

Pediatric acute ITP incidence ranges from 1.9 to 6.4/100,000 children per year, while adult ITP incidence is 1.6/100,000 per year.
Prevalence
data are few; only one population (in Oklahoma):
A prevalence of 11.2/100,000 people overall
Children (under the age of 16): 8.1/100,000, with an average age of 6 years; adults (over the age of 16): 12.1/100,000, with an average age of 55 years


Pathophysiology and Etiology 
IgG autoantibodies against platelet membrane glycoproteins IIb/IIIa cause reticuloendothelial phagocytes to consume platelets more quickly. Additionally, CD8+ T lymphocytes can destroy platelets by cell-mediated means.
Megakaryocyte maturation is hampered by autoantibodies, which reduces output.
Desialylated platelet clearance that is Fc-independent has been hypothesized as the mechanism underlying resistance to treatments that target the conventional FC-dependent pathway.
In patients taking immune checkpoint inhibitor medication, there is an association


Risk Elements 
Thrombocytopenia due to autoimmunity (such as Evans syndrome)
Drug side effects (e.g., quinidine, vancomycin, penicillin, sulfonamides) Common variable immunodeficiency (CVID)
Helicobacter pylori, hepatitis C, HIV, CMV, varicella zoster, measles, rubella, influenza, EBV, and Whipple illness are among the infections.
A side effect of vaccination. The danger of receiving a live virus vaccination is lower than the chance of contracting a virus naturally: the MMR vaccine doses have a risk of 2.6/100,000 versus a risk of 6 to 1,200/100,000 for measles or rubella.
A side effect of bone marrow transplantation
Connective tissue illness, such as antiphospholipid antibody syndrome and systemic lupus erythematosus
Disorders of lymphoproliferation

Diagnosis 
The basic criteria for diagnosing ITP continue to include a thorough history, physical examination, assessment of the CBC, and peripheral blood smear.


Providing History Frequently asymptomatic; discovered by chance on a routine CBC
Posttraumatic bleeding starts to happen at levels between 40 and 60 109/L. Bruising propensity, epistaxis, menorrhagia, and gingival bleeding are frequent with counts 30 109/L. With a platelet count less 20 109/L, spontaneous bleeding is possible. Female sex and exposure to NSAIDs have been connected with bleeding. Intracerebral bleeding is uncommon and may occur with counts 20 109/L and accompanied trauma or vascular lesions, resulting in neurologic symptoms.

clinical assessment 

It's typical to have ecchymoses, petechiae, epistaxis, and gingivorrhagia.
There could be abnormal uterine bleeding.
Buccal mucosal hemorrhagic bullae are a sign of a severe, acute thrombocytopenia.
Splenomegaly, hepatomegaly, lymphadenopathy, and other congenital illness stigmata were not present.


Differential diagnosis includes: acute leukemia; thrombotic thrombocytopenic purpura; hemolytic uremic syndrome; factitious platelet clumping on peripheral smear; sepsis-related thrombocytopenia; myelodysplastic syndrome, particularly in older patients; decreased marrow production due to cancer, drugs, viruses, and megaloblastic anemia; post-transfusion; gestational thrombocytopenia; immune neona


Initial test results from the laboratory and imaging
CBC with peripheral smear and differential:
- A single instance of a reduced platelet count of 100 to 109/L or more.
- Standard morphology of red and white blood cells
Consider the following if a patient has ITP-typical history, exam, CBC, and peripheral smear results:
PT/PTT is typical.
- Serologies for HIV, hepatitis B, and hepatitis C infections are advised in adults.
– Immunoglobulin levels are frequently measured in pediatric ITP to rule out CVID.
– Antiplatelet, antinuclear, antiphospholipid antibodies; H. pylori testing; thrombopoietin; platelet parameters; direct antiglobulin test; reticulocyte count; urinalysis; and thyroid function tests are additional procedures that are not required for patients with typical ITP presentation. If a patient with thrombocytopenia also exhibits any of the following conditions: - Fever, arthralgia, lymphadenopathy, family history of bleeding disorders, risk factors for HIV, or abnormalities in other cell lines - Additional research should be undertaken.
Additional tests not currently advised by the recommendations:
- The sensitivity and specificity of using reticulated platelets or immature platelet function (RP/IPF) to make a differential diagnosis in patients of ITP are 83% and 75%, respectively.
Testing for platelet antibodies like GPIIb/IIIa and GPIb/IX in ambiguous instances has a sensitivity and specificity of 90% and 78%, respectively.


Other/Diagnostic Procedures
Imaging is not required.
Bone marrow aspiration/biopsy - Not required for diagnosis in children or adults - Can be taken into consideration for a patient exhibiting atypical symptoms, such as fever, weight loss, and various blood count abnormalities
Interpretation of Tests

Normal to abundant megakaryocytes with normal erythroid and myeloid precursors can be seen in the marrow when compared to the peripheral smear, which shows normal red and white cells with large or giant platelets but less of them.


Management 
Management is based on both hemorrhagic symptoms and platelet count.
Current evidence-based recommendations state that newly diagnosed individuals with a platelet count of less than 30 109/L should get treatment.

Instead of a normal count, the major objective is to reach a platelet count that is associated with acceptable hemostasis.

Unless the patient has a platelet count below 20 109/L and is at danger of bleeding, outpatient care is recommended.

Admit people who are bleeding actively.

First Line of Medicine

First-line pediatric treatment:
 Platelet count is unimportant for monitoring children with no or minimal bleeding (bruising and petechiae solely without mucosal leakage).
For kids who are bleeding heavily
A single dosage of 0.8 to 1.0 g/kg intravenous immunoglobulin (IVIG), particularly when a more faster rise in platelet count is required. Given the danger of anaphylaxis, do not provide to individuals with IgA deficiency.

 A single dose of anti-Rho(D) immunoglobulin (anti-D), 50 to 75 g/kg for nonsplenectomized children who are Rh-positive, with negative direct antiglobulin test. A brief course of corticosteroids (e.g., PO prednisone 2 mg/kg/day for 2 weeks with 3 weeks taper). Use with caution in kids who have low hemoglobin levels or signs of hemolysis.
– Second and other therapies for children and teenagers with ITP
Rituximab (Rituxan) 375 mg/m2 once a week for 4 weeks, high-dose dexamethasone 0.6 mg/kg/day for 4 days every 4 weeks, splenectomy for chronic or persistent ITP Azithromycin, cyclosporin A, danazol, mycophenolate mofetil, anti-CD52 monoclonal antibody, and interferon are other medications lacking sufficient data.
Clinical trials in phase 3 have demonstrated that thrombopoietin receptor agonists produce positive effects in kids with chronic ITP.
First line, adult ITP for adults
Patients who have just been diagnosed and have a platelet count below 30 109/L are advised to seek treatment.
Dexamethasone 40 mg/day for 4 days straight is preferable to IVIG or lengthier doses of steroids since it has a similar level of efficacy and fewer side effects.
If using corticosteroids is not advised:
IVIG: once, 1–2 g/kg; repeat as necessary OR
Anti-D: For Rh+, non-splenectomized patients, administer 50 to 75 g/kg once, repeating as necessary. Use of anti-D should be avoided in patients with low hemoglobin levels or signs of hemolysis (1).
- Adult ITP, second line
For patients who failed corticosteroid treatment, splenectomy (1)[B]
Eltrombopag (Promacta), 50 mg/day PO OR romiplostim (Nplate), 1 g/kg SC weekly are two thrombopoietin receptor agonists for patients for whom splenectomy is contraindicated and who are at risk of bleeding.
Rituximab, 375 mg/m2 IV once a week for 4 weeks, for patients at high risk of bleeding who have not responded to one line of treatment or who have undergone splenectomy Azithromycin, cyclosporine A, cyclophosphamide, danazol, dapsone, mycophenolate mofetil, and vincristine are additional medications to take into account.
Patients with platelet counts greater than 30 109/L who are asymptomatic following splenectomy do not need to be treated.
 The FDA just authorized:
In addition, Fostamatinib (Tavalisse), 100 mg twice daily, and Avatrombopag (Doptelet), 5 daily doses (60 mg if baseline platelet count is below 40 109/L or 40 mg if 40 to below 50 109/L).

ITP during pregnancy Unrelated to ITP, preeclampsia or gestational thrombocytopenia may result in thrombocytopenia.
– First-line treatments include corticosteroids or IVIG, both of which are regarded as safe.
– Don't use cyclophosphamide or danazol. The mode of delivery should be based on obstetric indications, and ITP therapy at the moment of birth is based on maternal bleeding risks. Neonatal thrombocytopenia can be brought on by platelet autoantibodies that pass through the placenta.
– If the platelet count is greater than 50 109/L, a cesarean section may be considered.
– Between two and three weeks before delivery, prednisone and/or IVIG may be recommended.
Antivirals should be investigated before other treatments for ITP caused by HIV.
– If treatment is necessary, the first-line choices include corticosteroids, IVIG, or anti-D, whereas the second-line option is splenectomy.

 ITP brought induced by HCV
- Before pursuing additional forms of treatment, antivirals should be considered (1).
– If treatment is needed, IVIG is the first course of action.
– TPO mimetics are licensed for HCV-related ITP because, according to recent research, they raise platelets to the level necessary to start antiviral medication.
ITP and H. pylori - Test patients for H. pylori; if positive, eradication therapy would be recommended.
ITP brought on by immune checkpoint inhibitor therapy: If this is suspected, discontinue using the offending substance and follow the directions above for first-line treatment of ITP in adults.
Emergency treatment includes IV corticosteroids (e.g., IV methylprednisolone, 1 g/day for 3 doses) with caution in patients with GI bleeding and/or IVIG 1 g/kg; repeat the following day for count 50 109/L, massive hematuria, internal hematoma, or who need emergent surgery.
– For substantial bleeding, platelet transfusions with IVIG may also be taken into account.
– Other potential agents include: In addition to encouraging hemostasis, recombinant factor VIIa raises the risk of thrombosis. Only adjuvant therapies, such as aminocaproic acid and tranexamic acid, have been shown to be effective in randomized studies. There have been cases of emergency splenectomy.


Referral Hematology consultation is advised for people who are bleeding suddenly or who don't respond to standard treatments.


Operative Techniques Splenectomy

Even in patients with severe thrombocytopenia, the mortality rate is relatively low (less than 1%).
Prior to splenectomy, patients must receive the following vaccinations: polyvalent pneumococcal vaccine, quadrivalent meningococcal vaccine, one-time Haemophilus influenzae type b (Hib) vaccine. Patients should also consider taking penicillin or erythromycin as a lifelong preventive antibiotic.
Prior to surgery, the platelet count should be increased to at least 20 109/L.
The reported 5- to 10-year effectiveness for all patients is around 65%.
In medically qualified patients, laparoscopic splenectomy offers improved short-term outcomes and comparable long-term outcomes to surgical splenectomy.


Patient Follow-Up Monitoring
Weekly platelet counts for people taking steroids and monthly counts for people who are stable are suitable. After 10 days of starting medication, platelet counts are advised if a short-course of dexamethasone is chosen. If the platelet count increment falls short of the desired level, a second short course is advised.


Diet – There is insufficient research to support the use of an anti-inflammatory diet in ITP.
Garlic, ginger, Ginkgo biloba, and saw palmetto are among the substances and dietary supplements that can significantly increase bleeding.
Evening primrose oil, fish oil, feverfew, ginseng, licorice, soy, vitamin C, vitamin E, and wintergreen are some foods and supplements that may suppress platelets.

Alfalfa, angelica, anise, asafetida, aspen bark, birch, black cohosh, celery, chamomile, cinnamon, dandelion, fenugreek, heartsease, horse chestnut, meadowsweet, poplar, prickly ash, Quassia, sarsaparilla, sweet birch, sweet clover, and willow bark are a few examples of foods and supplements that


Modification of Lifestyle 
Avoid contact sports; modify activity; avoid anticoagulants, aspirin, and other platelet-inhibiting medications; and NSAIDs.


Acute ITP prognosis: 80–85% of patients fully recover in 2 months.
15% of people get chronic ITP.
Chronic ITP: 10–20% of patients experience spontaneous recovery.
- May experience spontaneous remissions and relapses (5%) and continue to have decreased platelets for months to years.
10% of cases are refractory (medical treatment and splenectomy fail).

Complications of thrombocytopenia include a 1% death rate from cerebral bleeding and significant blood loss.
For instance, adverse effects of corticosteroids, anaphylaxis and renal failure from IVIG, hepatotoxicity with eltrombopag, cases of progressive multifocal leukoencephalopathy from rituximab, hemolysis from anti-D, and septicemia in individuals who have had their spleens removed.

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