Disorder of Primary Hemostasis

Chapter 26

Platelet Satellitism

Platelets clump around neutrophils that leads to pseudothrombocytopenia (falsely low count)

Tests to Classify Bleeding Disorders

1. Automated platelet count (quantitative analysis)

2. Peripheral smear inspection: assess large/dysplastic platelets, clumping & platelet satellitism

3. PFA-100: automated function analyzer that screen for primary hemostasis. This replaces the traditional bleeding time test

4. PT & aPTT: should have normal result in primary hemostatic disorder

Thrombopoietin (TPO)

Growth factor produced primarily by the liver, some from spleen that tell BM to produce platelets

Thrombocytopenia {Causes}

Hallmark clinical sign is petechiae on the lower legs

• Deficient production due to impaired megakaryopoiesis

• Splenic sequestration, a large amount of blood gets trapped in the spleen, causing it to swell (splenomegaly). As a result, excessive circulating platelets are trapped at the spleen

• Increased destruction from immune-compromised

Myelophthisic (Infiltrative)

A severe type of bone marrow failure where normal marrow space is crowded out and replaced by abnormal cells, fibrosis, or tumors

• Leukemia, lymphoma, multiple myeloma

• Metastatic carcinoma, myelofibrosis

Thrombocytopenia {Diseases}

Myelophthisic

• leukemia, lymphoma, multiple myeloma, metastatic carcinoma, myelofibrosis

Aplasia

• Aplastic anemia (Fanconi’s)

• Amegakaryocytic thrombocytopenia

• Radiation (chemotherapy), drug effect

Ineffective Hematopoiesis

• Megaloblastic anemia (Pernicious)

• Liver disease

• Myelodysplastic syndrome (MDS)

• Paroxysmal nocturnal hemoglobinuria (PNH)

Congenital Thrombocytopenia Disorders (Quantitative Category)

1. Alport syndrome

2. Chediak-Higashi syndrome

3. Hermansky-Pudlak syndrome

4. May-Hegglin anomaly

5. TAR syndrome

6. Wiskott-Aldrich syndrome

Hypersplenism {Disorders}

Normal spleen sequesters (traps) 1/3 of platelets. Conditions that cause enlarge spleen include

• Liver cirrhosis

• Hematologic malignancies

• Portal vein thrombosis (clotting in the liver vein)

• Hemangiomas (vascular tumors trap & destroy platelets

Immune Thrombocytopenic Purpura (ITP)

• Autoantibodies attack own platelets, which causes isolated thrombocytopenia (normal RBC & WBC)

• Diagnosis of exclusion (no single test diagnosis)

• Symptoms include menorrhagia (heavy menstrual bleeding), epistaxis (nosebleeds), petechiae, easy bruising

• Vaccine such as measles & COVID-19 can cause ITP

ITP Laboratory Diagnosis & Treatments

Diagnosis

• Platelet count & blood smear to assess for large platelets and low count

• Viral testing to exclude Hepatitis C & HIV

• Antiplatelet antibody test, however it’s not specific

Treatments

• Corticosteroids: first-line (initial) treatment that suppress immune response

• IV IgG: plasma injection for IgG that block receptors of macrophages, extremely fast response

• Splenectomy: long-term option

• Rituximab: monoclonal antibody that target CD20 on B cells, option for recurring cases

Post-Transfusion Purpura (PTP)

• Anamnestic immune response (secondary reaction) from prior exposure to platelet antigen from blood transfusion or pregnancy

• Common in middle-age women who have had pregnancy, fetus has HPA-1a platelet antigen and the mother is negative. The antigens cross placenta and enter maternal circulation. Opposite can occurs and destroy fetus platelets as well (isoimmune neonatal thrombocytopenia)

Heparin-Induced Thrombocytopenia Thrombosis Syndrome (HITTS)

• Thrombocytopenia and thrombosis occurs 5-10 days after heparin exposure

• Heparin + PF4 (Not calcium/factor 4) → IgG antibodies → platelets activate → thrombosis → platelets consumption

• Discontinue heparin and switch to alternative anticoagulant

• 4T pretest probability scoring: intermediate 4-5, high: 6-8

Thrombotic Thrombocytopenic Purpura (TTP) {Treatment}

• Deficient in ADAMTS13 enzyme that is designed to cleave large vWF multimers → platelets aggregate & thrombi forms and obstruct small vessels

• Associate with microangiopathic hemolytic anemia (increased schistocytes, reticulocytes, LDH & indirect bilirubin)

• Treat by plasma exchange

• Pentad signs/symptoms:

  1. Fever

  2. Microangiopathic hemolytic anemia

  3. Thrombocytopenia

  4. Neurological abnormalities

  5. Renal dysfunction

Hemolytic Uremic Syndrome (HUS) {Treatment}

• Share many of the same symptoms with TTP

• Most common in children presents with diarrhea from E.coli/Shigella toxin

• Atypical due to deficiency of complement regulators & proteins

• Treat by fluid replacement, RBC & platelets transfusion

Disseminated Intravascular Coagulation (DIC)

• A non-immune thrombocytopenia due to excessive consumption of platelets that caused by sepsis, severe trauma

Pregnancy-Associated Thrombocytopenia

• Gestational thrombocytopenia: mild decrease of WBC in late pregnancy

• Eclampsia: hypertension & proteinuria in late pregnancy

• HELLP syndrome: hemolyze, elevated liver enzymes, low platelets. Associates with microangiopathic HA

Thrombocytosis {Primary vs Secondary}

• Primary thrombocytosis: abnormal platelet morphology and nonfunctional. Due to myeloproliferative neoplasm (MPN) from abnormal stem cell that produce excessive RBC including megakaryocyte

• Secondary thrombocytosis: normal & functional platelets, high platelets due to chronic inflammation/infection, or malignancy