A 13-year-old girl is brought to the pediatrician due to a 4-month history of heavy vaginal bleeding during menstrual periods. She endorses episodes of bleeding gums after brushing her teeth and experienced prolonged bleeding after tonsillectomy 6 years ago. Her mother states that she bled significantly during childbirth and that the girl’s older brother has similar symptoms including easy bruising. Vitals were stable and physical exam was not revealing. Laboratory studies show: Platelet count: 72,000/mm^3 Bleeding time: 14 min Prothrombin time: 12 secs (INR = 1) Partial thromboplastin time: 40 secs Blood smear demonstrates increased megakaryocytes and enlarged platelets. Platelets do not aggregate to ristocetin. Which of the following is the most likely diagnosis?

Idiopathic thrombocytopenic purpura (ITP)

A 23-year-old woman presents to the emergency department with a 3-day history of fever and headache. She says that the symptoms started suddenly after she woke up 3 days ago, though she has been feeling increasingly fatigued over the last 5 months. On presentation, her temperature is 102°F (38.9°C), blood pressure is 117/74 mmHg, pulse is 106/min, and respirations are 14/min. Physical exam reveals diffuse petechiae and conjunctival pallor and selected laboratory results are shown as follows: Bleeding time: 11 minutes Platelet count: 68,000/mm^3 Lactate dehydrogenase: 105 U/L Which of the following would also most likely be true for this patient?

Increased serum von Willebrand factor multimers

Large platelets on peripheral blood smear

Immune production of anti-platelet antibodies

Decreased platelet aggregation on platelet function studies

Increased prothrombin time and partial thromboplastin time

A 3-year-old girl is brought to her pediatrician because of a nosebleed that will not stop. Her parents say that she started having a nosebleed about 1 hour prior to presentation. Since then they have not been able to stop the bleeding. Her past medical history is remarkable for asthma, and she has a cousin who has been diagnosed with hemophilia. Physical exam reveals diffuse petechiae and purpura. A panel of bleeding tests are obtained with the following results: Bleeding time: 11 minutes Prothrombin time: 14 seconds Partial thromboplastin time: 32 seconds Platelet count: 195,000/mm^3 Peripheral blood smear shows normal cell morphology. Which of the following characteristics is most likely true about this patient?

Mutation in glycoprotein IIb/IIIa

Production of anti platelet antibodies

Production of antibodies against ADAMTS13

Decreased levels of von Willebrand factor

A 47-year-old woman presents for a routine wellness checkup. She complains of general fatigue and lethargy for the past 6 months. She does not have a significant past medical history and is currently not taking any medications. The patient reports that she drinks “socially” approx. 6 nights a week. She says she also enjoys a “nightcap,” which is 1–2 glasses of wine before bed every night. She denies any history of drug use or smoking. The patient is afebrile, and her vital signs are within normal limits. A physical examination reveals pallor of the mucous membranes. Her laboratory findings are significant for a mean corpuscular volume of 72 fL, leukocyte count of 5,300/mL, hemoglobin of 11.0 g/dL, and platelet count of 420,000/mL. Which of the following is the most likely cause of this patient’s thrombocytosis?

Chronic myelogenous leukemia (CML)

A previously healthy 38-year-old woman is brought to the emergency department by her husband because of left-sided weakness. As she was getting dressed this morning, she was suddenly unable to button up her shirt. When she showed her husband, he noticed that she seemed confused. She has a 3-year history of diabetes mellitus, for which she takes metformin. She had a knee operation 2 days ago. Her temperature is 38.9°C (102°F), pulse is 98/min, respirations are 17/min, and blood pressure is 138/85 mm Hg. She is confused and oriented only to person. Neurologic examination shows diminished muscle strength on the left side. There are scattered petechiae over the chest, arms, and legs. Laboratory studies show: Hemoglobin 7.5 g/dL Leukocyte count 10,500/mm3 Platelet count 40,000/mm3 Prothrombin time 15 seconds Partial thromboplastin time 36 seconds Serum Bilirubin Total 3.5 mg/dL Direct 0.3 mg/dL Urea nitrogen 35 mg/dL Creatinine 2.5 mg/dL Lactate dehydrogenase 1074 U/L A peripheral smear shows numerous schistocytes. Further evaluation is most likely going to show which of the following findings?

Decreased ADAMTS13 activity in serum

Enterohemorrhagic Escherichia coli on stool culture

Elevated fibrin degradation products in serum

Decreased megakaryocytes on bone marrow biopsy

A previously healthy 40-year-old woman comes to the physician because of a 3-day history of fever, headaches, and fatigue. She also reports a persistent tingling sensation in her right hand and numbness in her right arm that started this morning. Physical examination shows pallor, mild scleral icterus, and petechiae on her forearms and legs. On mental status examination, she appears confused and is only oriented to person. Laboratory studies show: Hemoglobin 11.1 g/dL Platelet count 39,500/mm3 Bleeding time 9 minutes Prothrombin time 14 seconds Partial thromboplastin time 35 seconds Serum Creatinine 1.7 mg/dL Total bilirubin 2.1 mg/dL A peripheral blood smear shows fragmented erythrocytes. Which of the following is the most likely underlying cause of this patient's condition?

Antibodies against double-stranded DNA

Absence of platelet GpIIb/IIIa receptors

A 12-year-old boy, otherwise healthy, presents with frequent nosebleeds and lower extremity bruising. His mother reports that his symptoms started about 2 weeks ago and have not improved. The patient received the Tdap vaccine 2 weeks ago. He has no current medications. The review of systems is significant for the patient having a stomach ache after winning a hamburger eating competition 2 weeks ago. The vital signs include: temperature 37.0°C (98.6°F), blood pressure 110/75 mm Hg, pulse 95/min, respirations 15/min, and oxygen saturation 99% on room air. On physical exam, the patient is alert and cooperative. The cardiac exam is normal. The lungs are clear to auscultation bilaterally. The lower extremities findings are shown in the image. Laboratory results are pending. Which of the following best describes the pathogenesis of this patient’s condition?

IgG autoantibodies against platelet glycoproteins

Shiga-toxin mediated damage to vascular endothelium, resulting in microthrombi formation

Systemic activation of clotting cascade resulting in platelet and coagulation factor consumption

Deposition of IgA immune complexes

Platelet disorders for USMLE Step 1: High-Yield Pathology Lessons

Primary Hemostasis - The First Responders

Goal: Form a weak platelet plug at sites of vascular injury.
Involves platelets, von Willebrand factor (vWF), and vessel wall.

Platelet Plug Formation: Adhesion, Aggregation, Fibrin

Clinical signs: Mucocutaneous bleeding (petechiae, epistaxis).
Labs: Prolonged bleeding time.

⭐ Glanzmann thrombasthenia: Autosomal recessive defect in GpIIb/IIIa. Leads to impaired aggregation. Patients present with a normal platelet count but significant bleeding.

Thrombocytopenia - The Platelet Plummet

Definition: Platelet count < 150,000/μL.
Etiology Overview:
- ↓ Production: Marrow failure (aplastic anemia), infiltration (leukemia), drugs (chemo), infection (HIV).
- ↑ Destruction: Immune (ITP, TTP, HIT) or non-immune (DIC, hypersplenism).
Clinical Signs: Petechiae, purpura, ecchymoses. Spontaneous bleeding risk ↑ if < 20,000/μL.

Petechiae and Purpura in Immune Thrombocytopenia (ITP)

⭐ Immune Thrombocytopenic Purpura (ITP): An acquired autoimmune disorder with isolated thrombocytopenia. Often triggered by a recent viral infection in children. Antibodies target platelet glycoproteins like GpIIb/IIIa.

Qualitative Disorders - A Dysfunctional Crew

Presentation: Normal platelet count, but ↑ Bleeding Time.
Bernard-Soulier Syndrome:
- Big Suckers: giant platelets (mild thrombocytopenia is common).
- Defect in GpIb receptor → impaired adhesion to von Willebrand factor (vWF).
Glanzmann Thrombasthenia:
- Defect in GpIIb/IIIa receptor → impaired aggregation.
- No platelet clumping in response to ADP, epinephrine, or collagen.
Acquired Causes:
- Aspirin: Irreversibly inhibits COX, leading to ↓ Thromboxane A₂ (TXA₂) synthesis.
- Uremia: Impairs both adhesion and aggregation functions.

⭐ The Ristocetin cofactor assay helps differentiate these disorders. Platelet aggregation is abnormal in Bernard-Soulier syndrome (as ristocetin requires vWF-GpIb interaction) but is normal in Glanzmann thrombasthenia.

Thrombocytosis - Overcrowded Traffic

Definition: Platelet count > 450,000/μL.
Reactive Thrombocytosis (More Common):
- Caused by an underlying condition driving cytokine release (e.g., IL-6).
- Etiologies: Post-splenectomy, iron deficiency anemia, malignancy, chronic inflammation or infection.
- Platelets are numerous but functionally normal.
Essential Thrombocythemia (ET):
- Myeloproliferative neoplasm (MPN) with autonomous platelet production.
- Key mutations: JAK2, CALR, MPL.
- Presents with thrombosis (arterial/venous), erythromelalgia (burning pain in hands/feet), or bleeding.

⭐ Despite high platelet numbers, paradoxical bleeding can occur when counts exceed 1 million/μL due to acquired von Willebrand syndrome, as platelets adsorb and clear large vWF multimers.

High‑Yield Points - ⚡ Biggest Takeaways

Immune Thrombocytopenic Purpura (ITP) involves IgG anti-GpIIb/IIIa antibodies, often post-viral in children.

Thrombotic Thrombocytopenic Purpura (TTP) results from ADAMTS13 deficiency, causing uncleaved vWF multimers and a classic pentad.

Hemolytic Uremic Syndrome (HUS) is typically due to Shiga-like toxin (E. coli O157:H7), causing a triad of MAHA, thrombocytopenia, and AKI.

Bernard-Soulier syndrome is a GpIb defect causing impaired adhesion and giant platelets.

Glanzmann thrombasthenia is a GpIIb/IIIa defect causing impaired aggregation.

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