Clinical Chemistry
Quantitative Platelet Disorders Thrombocytopenia
Vocabulary:
Thrombosis:
Stagnation of blood flow caused by:
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Arterial Disease
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or mechanical impedance disturbs the endothelial cell anticoagulant effect
Thrombosis leads to the formation of thrombus clot & hypercoagulable states
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Cascade:
Process of involving interlinked steps
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Hemostasis:
The cascade mechanism of stopping the bleeding from a blood vessel by forming a "plug" that closes up the damaged part of the blood vessel to control the bleeding.
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Primary Hemostasis:
Platelet adhesion to exposed collagen with the endothelium of the vessel wall
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Interaction results in clump of platelets (primary hemostatic plug or soft clot)
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The primary hemostatic plug temporarily stops bleeding, but it is fragile & easily dislodged from the vessel
What is Thrombocytopenia?
Definition: A decrease in the number of circulation platelets
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Thrombocytopenia: <50 x 10^9 /L
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Normal Reference Range: 150,000-450,000 platelets
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Clinical Evidence of Thrombocytopenia:
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Increased amount of petechiae​
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Hemorrhages
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Prolonged bleeding time
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Impaired clot retraction
What are the Causes of Thrombocytopenia?
Causes:
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Decreased platelet production in the bone marrow
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Decreased amount of megakaryocyte​
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Ineffective platelet production
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Disorders of distribution & dilution of platelets ​in the circulation
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Destruction of platelets

Levels of Thrombocytopenia
A Closer Look Into Thrombocytopenia
Let's take a closer look into major disorders/diseases associated to thrombocytopenia.
Fanconi's Anemia
Mechanism: Decreased # of Megakaryocytes
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Inherited Megakaryocytic Hypoplasia
Description:
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Decreased # of Megakaryocytes
May Hegglin Anomaly (MHA)
Mechanism: Decreased # of Megakaryocytes
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Acquired Megakaryocytic Hypoplasia
*NOTE: Also associated with Qualitative Platelet Disorders
Description:
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[See Qualitative Platelet Disorders for More Info]

Bernard-Soulier Syndrome
Mechanism: Decreased # of Megakaryocytes
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Acquired Megakaryocytic Hypoplasia
*NOTE: Also associated with Qualitative Platelets Disorders
Description: Rare inherited bleeding disorder
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[See Qualitative Platelet Disorders for More Info]
Wiskott-Aldrich Syndrome
Mechanism: Decreased # of Megakaryocytes
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Acquired Megakaryocytic Hypoplasia
*NOTE: Also associated with Qualitative Platelets Disorders
Description:
​
[See Qualitative Platelet Disorders for More Info]

Drug-Induced Thrombocytopenia
Mechanism: Ineffective Platelet Production
Description:
​

Di Guglielmo's Syndrome
(Erythroleukemia)
Mechanism: Ineffective Platelet Production
Description:
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Paroxysmal Nocturnal Hemoglobinuria (PNH)
Mechanism: Ineffective Platelet Production
Description:
​

Increased Destruction/Consumption
*The main thrombocytopenic disorders that needed to be studied & distinguished from.
Immune Thrombocytopenic Purpura (ITP)
Also known as Idiopathic Thrombocytopenic Purpura
Mechanism: Increased Platelet Destruction/ Consumption
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Immune (Autoimmune)
Description:
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Diagnosis of Exclusion
Immune Mediated platelet destruction following a recent infection
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​
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ITP
Pathogenesis:
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↑ bone marrow platelet production
Acute ITP (self limiting: 2-6 weeks)​​
Spontaneous remission in 80%
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Viral attachment & antigenic alteration of platelet membrane proteins
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Forms platelet autoantibodies (IgG) coating platelets & are removed by macrophages in the spleen
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Chronic ITP​ (Last months or years)
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Associated with systemic lupus erythematosus (SLE)
Clinical Presentation:
​
Target Presentation:
Acute ITP
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Occurs in children 2-6 years of age
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Often following viral infection(s)
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Rubella​
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Chickenpox
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Cytomegalovirus (CMV)
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Toxoplasmosis
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Chronic ITP​
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Occurs in adults 20-40 years of age
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Women are 3 times more than in men​
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Lab Test Results
↑ Mean Platelet Volume (MPV)
↓ Platelet count
↑ Marrow megakaryocyte
Normal Bleeding time
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Acute ITP
< 20,000 platelets
Chronic ITP
~55,000 platelets (not as severe)
Blood Smear: Schistocytes
Heparin Induced Thrombocytopenia (HIT)
Mechanism:
Increased Platelet Destruction/ Consumption
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Alloimmune
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Clearance of activated platelets & antibody-coated platelets by the reticuloendothelial system (RES)
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Description:
​Formation of antibodies that activate the platelets following heparin administration
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Most important & most frequent form of drug-induced thrombocytopenia
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HIT
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Thrombotic Thrombocytopenic Purpura (TTP)
Mechanism: Increased Platelet Destruction/ Consumption
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Non-immune
Description: Microangiopathic hemolytic anemia causing nonimmune hemolysis
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Lab Test Results
↑ Bleeding Time
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Blood Smear: Schistocytes
TTP
Pathophysiology:
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ADAMS-13 deficiency causing ↑ vonWillebrand factor
Clinical Presentation:
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Thrombocytopenia
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Anemia
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Fever
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Neurologic Symptoms
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Renal Dysfunction
Hemolytic Uremic Syndrome (HUS)
Mechanism: Increased Platelet Destruction/ Consumption
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Non-immune
Description:
​
​
Lab Results
↑ Bleeding time
Thrombocytopenia
↑Creatinine
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Blood Smear: Schistocytes
HUS
Pathogenesis:
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Shiga toxin-mediated hemolysis
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Infection of pathogenic E. coli 0157:H7 or another E.coli strain​​
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Clinical Presentation:
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Kidney Failure following E.coli infection
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Bloody Diarrhea
Target Population:
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Occurs often in children who ingested the toxin
Disseminated Intravascular Coagulation (DIC)
Mechanism: Increased Platelet Destruction/ Consumption
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Non-immune
Description: Inappropriate widespread clotting activation usually secondary to:
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trauma
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sepsis
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obstetric complications
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Lab Results:
↓PLT
↑ Bleeding Time
↑ PT
↑ PTT
↑ D-Dimer
↓Fibrinogen
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Blood Smear: Schistocytes
DIC
Pathogenesis:
​Uncontrolled thrombin & plasmin causing excess tiny clots & bleeding, respectively
Clinical Presentation:
​
Target Population
Sources:
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Ahmed, I., Majeed, A., & Powell, R. (2007, September). Heparin induced thrombocytopenia: Diagnosis and management update. Retrieved June 09, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600013/
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Dirty Medicine. (2017, February). Bleeding Disorders (ITP vs TTP vs HUS vs DIC) || USMLE [Youtube Video]. Retrieved from https://www.youtube.com/watch?v=U3VbjS7WqOE&t=65s
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Heikal, N. (2017). Paroxysmal Nocturnal Hemoglobinuria: Rare but Real [PDF]. Retrieved June 09, 2020, from https://arup.utah.edu/media/heikal-pnh-2017/lecture-slides.pdf
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Jhang, J. S., (2006). Qualitative and Quantitative Platelet Disorders [PDF]. Retrieved June 09, 2020, from http://www.columbia.edu/itc/hs/medical/selective/AdvClinicalPathology/2006/lecture/jhang10-23_Blood%20Component%20Therapy.pdf
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George, J., & Aster, R. (2009). Drug-induced thrombocytopenia: Pathogenesis, evaluation, and management. Retrieved June 09, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413903/
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LAB CE. (2001). Increased Platelet Destruction. Retrieved June 08, 2020, from https://www.labce.com/spg280961_increased_platelet_destruction.aspx
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LaPelusa, A. (2019, October 12). Physiology, Hemostasis. Retrieved June 06, 2020, from https://www.ncbi.nlm.nih.gov/books/NBK545263/
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Mates, M. (2016). Hematology review [PDF]. Retrieved June 09, 2020, from https://www.studocu.com/row/document/aga-khan-university/haematology/lecture-notes/hematology-review/4664171/view