2 Thrombocyte Immunology

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Platelet/Thrombocyte

Immunology
Yudy Tjahjono, M.Sc.Biol.
Composition of Blood
Platelet / Thrombocyte
150.000-400.000/ml
Below 150.000 → Thrombocytopenia
Derived from Megakaryocytes
Resting and activated
Phagocytosis by Platelet

Platelets in lower vertebrate were able to


ingest live bacteria (sign: X) as well as latex
beads (0.5-3 μm in diameter) and kill the
bacteria. Mammals?? Human??
Nagasawa et al., Front. Immunol. 2014
Role of Platelet in cancer metastasis:
“positive and negative” aspect

start

EMT : Epithelial to mesenchymal transition


(increased migration, differentiation and invasion)
Schlesinger M., Journal of Hematology & Oncology (2018) 11:125
Platelet aggregation-invivo
Clotting factors and disorders
Clotting factor disorders can
causes: Haemorhage / Bleeding

• Majority caused by:


- Fibrinogen,
- Thrombin,
- vWF

Indirect defective function of Platelet


Diagnostics: Bleeding time

Duke Methods-
Earlobe/Fingertips
normal range: 1-3 min
Ivy Methods-Hand
Mielke Methods-
Hand+armband
normal range: 5-10 min
Diagnostic: Prothrombin Time (PT) and
PTT (Partial thromboplastin time)
Hemostasis-Coagulation:
PTT (Partial Thromboplastin Time)
• Measure intrinsic
coagulation factor
(integrity of the intrinsic
system: Factors XII, XI,
VIII, IX Add Kaolin,
Phospolipid, Ca2+
(37°C)➔ Blood Clot
• Fast. Normal range: 35
Sec.
• Detect: Factors XII, XI,
VIII, IX deficiency
Hemostasis-Coagulation:
PT (Prothrombin time)
• Measure extrinsic
coagulation factor
(initiated by exposure to
tissue factors)
• Add Thromboplastin and
Ca2+ (37°C)➔ Blood Clot
• Very Fast. Normal range:
11-15 Sec.
• Detect: factors VII, X, V,
prothrombin,
fibrinogen,vitamin K
deficiency
Haemorhage theraphy
• Clotting factor concentrates
• Avoid medical components which caused
platelet disruption.
Platelet Surfaces
Platelet Function Test-TAT
Platelet Function Test-TAT

Agonist:
Activate Platelets
Collagen: General
Aggregation Ability
ADP: measure
GPIIb/IIIa ability
(fibrinogen)
Ristocetin: measure
GPIb ability (VWF)
Platelet immunology Test-MAIPA
Monoclonal Antibody Mobilization of Platelet
Antigens
Platelet Antigens
Allo vs Autoimmunity
• Autoimmunity: Immunological reaction
caused by immunological components
(antigen, cells, Ig’s, etc.) inside the body

• Alloimmunity: Immunological reactions


caused by immunological components
from other individuals with the same
species.
Fetal/neonatal alloimune
thrombocytopenia (FNAIT)
• a common cause of severe isolated
thrombocytopenia in the fetus and the
newborn (HPA-1a Positive), occurs in 1 in
500 to 1 in 5000 live births.
• Hemorrhage, Bruises, Hematoma
Fetal/neonatal alloimune
thrombocytopenia (FNAIT)

TREATMENT: IVIG, NSAID, Corticosteroids


Autoimmune Thrombocytopenia
(ITP/idiopathic thrombocytopenic
purpura)
• ITP is caused by autoantibodies to platelets.
• The antigenic target : GP IIb/IIIa complex. Platelets
with antibodies on their surface are trapped in the
spleen, where they are efficiently removed by
macrophages.
• The mechanism of origin of these antibodies is not
known. These antibodies may be directed toward
viral antigens and then cross-react with platelet
antigens. They persist because of the failure of
immune surveillance mechanisms to repress these
antibodies.
• blood cell count: thrombocytopenia, anemia
and/or neutropenia.
• Findings on peripheral blood smear are as
follows:
The morphology of red blood cells (RBCs) and
leukocytes is normal
The morphology of platelets is typically normal,
with varying numbers of large platelets
Bernard-Soulier Syndrome
Glanzmann's thrombasthenia
• Autosomal Recessive
• BSS: Defect GPIb/IX/V
→vWF Receptor
• GT: Defect GpIIb/IIIa ➔
Fibrinogen receptor
Diagnosis Glanzmann/BSS
• The platelet count and coagulation tests
should be normal
• The red blood cell count may be decreased
due to bleeding and/or concomitant iron
deficiency.
• The bleeding times should be prolonged.
• Flow cytometry and monoclonal antibodies
(MAIPA) confirm the antibodies/antigen
• TAT…..
Diagnosis Glanzmann/BSS
TAT
Therapy GT/BSS:
•preventive measures such as avoidance of
antiplatelet agents (e.g., aspirin and NSAIDs)
•iron or folate supplementation for anemia, and
vaccination for hepatitis B due to the infectious risks
associated with multiple transfusions.
•Patients with GT who are bleeding require platelet
transfusion.
•Recombinant coagulation factor VIIa or fibrinogen
was approved by the FDA in July 2014 for bleeding
episodes and perioperative management in patients
with GT refractory to platelet transfusions, with or
without antibodies to platelets.
Platelet Surfaces
END

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