platelets disorders
TRANSCRIPT
Quantitative Platelets Disorders
Iqra YasinResident, Obs & Gyne Unit I
SIMS/Services Hospital, Lahore
Introduction
• The platelets arise from the fragmentation of the cytoplasm of megakaryocytes in the bone marrow– circulate in blood as disc-shaped anucleate particles
for 7-10 days.
• Platelets are responsible for primary hemostatic function
• Normal Count is 150,000/µl to 400,000/µl
ClassificationPl
atel
ets D
isord
ers
Quantitative
Thrombocytopenia(< 150,000/µl)
Decreased Production
Increased Consumption/Destruction
Splenic Sequestration
Pseudo
Aggregates in specimen (rule out on peripheral
smear)
Dilutional
Thrombocytosis(> 400,000/µl)
Qualitative
Inherited (rare)
Acquired (common)
Thrombocytopenia(Count < 150,000/µl)
Failure of Production Platelet Consumption/Destruction
Splenic Sequestation
Bone Marrow suppression Gestational Thrombocytopenia Liver Diseases
Drug Induced Immune Thrombocytopenia• Primary • Secondary
• SLE• Antiphospholipid
Syndrome• Drug induced(HIT)• Infection(HIV, EBV)
Portal HTN
Aplastic Anemia Non immune Thrombocytopenia• DIC• TTP/HUS• Preeclampsia(HELLP
syndrome)• Acute Fatty Liver of Pregnancy
Hepatic or Portal vein thrombosis
Infection(parvo B19) Spleenomegaly
Bone Marrow Infiltration Myeloprolifrative Disorders
(Non-)Hematological Malignancies Lymphoproliferstive Disorder
Severe Vit B12 and Folate Deficiency
Storage Diseases
Tropical infections (Malaria)
Evaluation of Patient with Thrombocytopenia
• Presence of current/previous bleeding problems– Mucocutaneous bleeding
• Skin lesions• Epitaxis, bleeding Gums, menorrhagia
• Past History– HIV, HBV, HCV, SLE and other systemic problem
• Obstetrical History– Recurrent abortion (Antiphospholipid syndrome)
• Family History– Hematological Problems
• Others– Drug, alcohol, tranfusion
Evaluation of Patient with Thrombocytopenia
• Examination– Petechiae(<2 mm), Purpura(2-10 mm), Ecchymosis (> 10 mm)– Features of CLD, SLE– Splenomegaly (CLD versus ITP)
• Investigations– CBC ( decreased platelet count)– Peripheral smear
–
Red cell Fragmentation DIC, Microangiopathies
Hypersegmented neutrophils Vit B 12 deficiency
WBC/ RBC abnormalites Underlying bone marrow disease
Normal ITP/Gestational thrombocytopenia
Evaluation of Patient with Thrombocytopenia
• Specific Investigations
ANA, SLE
Lupus Anticoagulant, anti cardiolipin antibodies Antiphospholipid Syndrome
D-Dimer, coagulation screening DIC
vWF-cleaving protease deficiency (ADAMTS 13 activity) TTP
Serum Urate level Preeclampsia, HELLP syndrome, Acute Fatty Liver of Pregnancy
Gestational Thrombocytopenia• 70 % of cases of thrombocytopenia at delivery
• Exact etiology unknown
• Suggested mechanisms includes– Dilutional– Reduced life span– Increased platelet activation in pregnancy in placental circulation
• Differentiated from ITP– Develop late in pregnancy(3rd trimester)– No Pre-pregnancy history of bleeding with normal Platelet count– Return to normal count within 7 days of delivery
Gestational Thrombocytopenia
• Investigation– Normal peripheral smear and bone marrow
examination with low platelet count
• Management– No treatment required during pre-pregnancy and
antenatal period– During labor and delivery and postnatal care
• If ITP not excluded, treat as case of ITP• Otherwise, no specific treatment required
Autoimmune Thrombocytopenia (AITP)
• 3 % of cases of thrombocytopenia at delivery
• Most common cause of thrombocytopenia in 1st Trimester
• Mechanism– Autoantibodies against Platelet surface glycoproteins leading to destruction in
RES
• Investigation– Normal peripheral smear and bone marrow examination with low platelet count– Normal other specific investigations– Platelets-associated IgG or glycoprotein-associated antibodies are not reliable
diagnostic tools in suspected case of AITP
Autoimmune Thrombocytopenia (AITP)
• Maternal Risks– Count < 20,000/µl(severe thrombocytopenia) at
any gestation and < 50,000/µl at delivery– associated high risk of spontaneous bleeding
antenataly and during delivery
• Fetal Risks– IgG antibodies crosses the placenta leading to
fetal thrombocytopenia(<2 % cases)
Autoimmune Thrombocytopenia (AITP)
• Management– Prepregnancy period
• Optimize the patient and consider for splenectomy• Discuss fetomaternal risk associated with ITP and side
effects of drugs given in ITP during pregnancy
– Antenatal Period• AIMS:
– To treat the maternal symptoms of hemorrhage at any stage of pregnancy
– To achieve a safe platelet count at delivery (> 50,000/µl)
Autoimmune Thrombocytopenia (AITP)
• Antenatal Period– To Whom Treatment should be given?
• If symptoms occur or platelet count <20,000/µl at any gestation and < 50,000/µl at delivery even if asymptomatic
– Treatment options• Steroids (Prednisolone 1mg/kg/day)• IVIG ( 1g/Kg for 1-2 days- Peak response at 4-5 days with total duration of response
3-4 weeks)• Splenectomy in refractory cases in 2nd trimester or occasionally in 3rd trimester during
delivery + prophylactic penicillin• Anti-CD20 monoclonal antibodies (Rituximab) and anti-D Ig in refractory cases as an
alternative slpenectomy• Azathioprine in non-responsive cases• Inform pediatrician and anesthetic about the delivery
Autoimmune Thrombocytopenia (AITP)
• During Labor and delivery
– Platelets should be available if < 50,000/µl but transfused only if bleeding
– Avoid epidural analgesia if count <80,000/µl– C-section no benefit over vaginal delivery– Count >50,000/µl safe for vaginal delivery (BCSH and
ASH guidelines)– Avoid traumatic delivery, fetal scalp electrodes and
fetal skull sampling
Autoimmune Thrombocytopenia (AITP)
• Post-natal Period
– Repair the episiotomy and tear promptly– Send cord sample for platelet count– Follow baby platelet count for few days if initial count is low– If baby is symptomatic or count < 20,000/µl then consider for
IVIG– If bleeding starts give platelet transfusion– Vaccination against pneumoccocus, Hib, Menningoccocus to
the mother– Avoid NASID as Postnatal analgesia
Thrombocytosis
Essential ( Primary)• Essential thrombocytosis (a
form of myeloproliferative disease)
• Other myeloproliferative disorders such as– chronic myelogenous
leukemia, – polycythemia vera,– myelofibrosis
Reactive ( Secondary)
• Inflammation
• Surgery (which leads to an inflammatory state)
• Hyposplenism (decreased breakdown due to decreased function of the spleen)
• Splenectomy
• Asplenia (absence of normal spleen function)
• Iron deficiency anemia or hemorrhage
Clinical Manifestation of Thrombocytosis
Constitutional symptoms • 20-30% of patients
• Weight loss is unusual.
• Other symptoms include sweating, low-grade fever, and pruritus.
Bleeding Symptoms• > 100,000/µl due to
abnormal function of platelets
• GI –main site
• Other sites of bleeding include the skin, eyes, gums, urinary tract
Clinical Manifestation of Thrombocytosis
Thrombotic Symptoms• Headache/Migraine• TIA• Visual Disturbance
• Microvascular occlusion of the toes and fingers– digital pain; – gangrene; or – Erythromelalgia (burning pain
and dusky extremity congestion)
• Thrombosis of large veins and arteries
• occlusion of the leg, coronary, and renal arteries.
• Venous thrombosis of the splenic, hepatic, or leg and pelvic veins may develop.
• Pulmonary hypertension
Clinical Manifestation of Thrombocytosis
Pregnancy complications• Recurrent Spontaneous
abortions
• Placental Infarction– IUGR– Fetal death
Thrombocytosis
• Diagnosis
– Platelet count > 400,000/µl– Megakaryocytic hyperplasia– Splenomegaly (40-50 % cases)– Thrombotic/Bleeding complication– CRP, fibrinogen, IL-6 (secondary thrombocytosis)
Thrombocytosis
• Management– Prenatal period
• Multidisciplinary approach• If symptomatic, consider plasmapheresis• If thrombosis occur, low dose aspirin/heparin• Hydroxyurea• IFN-alpha (limited experience), antagonize the effect of PDGF
– Labor and Delivery• Maintain vigilance for PPH