Platelet Disorders and Vascular Bleeding Abnormalities

Comprehensive practice flashcards covering platelet disorders, thrombocytosis, thrombocytopenia, coagulopathies, myeloproliferative neoplasms, and vessel wall defects based on the lecture by Dr. Aman Gupta.

How is ecchymosis clinically defined?

Ecchymosis refers to bruises that are often many, large, or deep.

What is hemarthrosis, and what clinical signs accompany it?

Bleeding into the joints, which presents with pain, swelling, or tightness.

What clinical terms describe blood in the urine, black tarry stool, and fresh blood in stool?

Hematuria (blood in urine), Melena (black tarry stool), and Hematochezia (fresh blood in stool).

What is epistaxis?

Spontaneous nosebleeds.

What is a characteristic clinical sign of bleeding disorders in infants?

Unexplained irritability.

What is subarachnoid hemorrhage?

Bleeding into the space that surrounds the brain.

What is intracerebral hemorrhage?

A hematoma inside the brain parenchyma, occurring with or without extension of blood into the ventricles.

In the provided brain bleed diagram, which bleed types correspond to letters A, B, and C?

A is an epidural bleed, B is a subdural bleed, and C is an intracerebral hemorrhage.

Where does a subdural bleed collect relative to the meninges?

In the subdural space, situated between the dura mater and the arachnoid mater.

Identify the sequential layers of the meninges and their spaces from the skull bone down to the brain.

Bone of skull, epidural space, dura mater, subdural space, arachnoid mater, subarachnoid space, pia mater, and brain.

What ocular condition is shown in this clinical image?

Hyphema (blood pooling in the anterior chamber of the eye).

Into which anatomical structures of the eye does blood move during a hyphema?

The conjunctiva (white part), cornea (clear dome-shaped window at the front), and iris (colored part).

What visual acuity symptom is caused by hyphema?

Blurred or distorted vision.

What causes nausea and vomiting in a patient presenting with hyphema?

An autonomic response triggered by an acute increase in intraocular pressure.

What is the normal reference range for circulating platelet counts?

$150 - 400 \times 10^3\,\text{platelets}/\mu\text{L}$.

What quantitative platelet threshold defines thrombocytosis?

$> 450{,}000\,\text{platelets}/\mu\text{L}$.

What platelet count threshold defines thrombocytopenia?

$< 150{,}000\,\text{platelets}/\mu\text{L}$.

What are the three primary physiological functions of platelets?

Platelet plug formation (hemostasis), thrombosis, and wound healing.

How do Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) typically appear in bleeding caused solely by thrombocytopenia?

Both PT and APTT are normal.

Which vascular structures are most commonly involved in spontaneous bleeding secondary to thrombocytopenia?

Small blood vessels, particularly those of the skin and mucous membranes.

According to the platelet count classification table, what clinical presentation occurs at a platelet count of $20{,}000-50{,}000\,\text{platelets}/\mu\text{L}$?

Easy bruising and aggravated post-traumatic bleeding.

At what platelet count threshold does spontaneous bleeding typically begin to manifest?

$< 20{,}000\,\text{platelets}/\mu\text{L}$.

What is the normal reference range for Duke's method of bleeding time measurement?

$2-5\,\text{minutes}$.

What modern automated instrument has replaced bleeding time for screening platelet dysfunction?

Platelet Function Analyzer.

Which agonists are routinely utilized in laboratory tests of platelet aggregation?

Thrombin, ristocetin, and related activating agonists.

What size criterion defines petechial hemorrhages?

$1\,\text{to}\,2\,\text{mm}$ hemorrhages into the skin, mucous membranes, or serosal surfaces.

What size criterion defines purpuric hemorrhages?

$3-5\,\text{mm}$ hemorrhages.

What erythematous lesions on the soft palate are shown in this clinical image?

Forchheimer's sign (Forscheimer's sign).

What mucosal lesions of the buccal mucosa are indicated in this figure?

Koplik spots.

Which organs produce thrombopoietin to stimulate megakaryocytopoiesis?

The kidneys and the liver.

Trace the cellular developmental sequence of thrombopoiesis from the myeloid stem cell.

Myeloid stem cell $\rightarrow$ Megakaryoblast $\rightarrow$ Megakaryocyte $\rightarrow$ Platelet precursor extensions $\rightarrow$ Platelets.

How do megakaryocytes release platelets into the bone marrow vasculature?

Megakaryocytes extend proplatelet projections through sinusoidal endothelial cells, where shear flow fragments them into individual circulating platelets.

What is the average lifespan of circulating platelets in peripheral blood?

$8\,\text{to}\,9\,\text{days}$.

What percentage of the body's total platelet pool is normally sequestered in the spleen?

$30\%\,\text{to}\,35\%$.

To what percentage can splenic platelet sequestration rise in the presence of splenomegaly?

$80\%\,\text{to}\,90\%$.

Why do massive blood transfusions lead to dilutional thrombocytopenia?

With prolonged storage of banked blood, the number of viable platelets decreases, diluting circulating platelets when transfused in large volumes.

What somatic gene mutation is commonly associated with overactive hematopoiesis in primary thrombocytosis?

Somatic mutation in $JAK2$.

What are the three primary myeloproliferative disorders causing primary thrombocytosis?

Polycythemia vera, Essential thrombocythemia, and Idiopathic myelofibrosis.

What are four common causes of secondary thrombocytosis in pediatric patients?

Chronic inflammation, infection, iron deficiency, and tissue damage.

What cellular mechanism explains thrombocytosis in Kawasaki disease?

Defective platelet apoptosis.

What proportion of thrombocytopenia cases are primary versus secondary?

Primary cases account for $80\%$, while secondary cases account for $20\%$.

What type of neoplasm is Polycythemia vera, and which hematopoietic lineage predominates?

A rare chronic myeloproliferative neoplasm (chronic leukemia) where all three cell lines are abnormal, but the erythroid lineage is predominant.

Why do patients with Polycythemia vera frequently experience intense itching after warm water or heat exposure?

Histamine release triggered by heat exposure.

What joint and extremity symptoms occur in Polycythemia vera?

Gouty arthritis (or toe joint pain) and burning sensations in the hands or feet.

What is Budd-Chiari syndrome?

Hepatic venous outflow obstruction.

What clinical triad characterizes Budd-Chiari syndrome?

Painful hepatomegaly, ascites, and liver dysfunction.

List five recognized causes of Budd-Chiari syndrome.

Hypercoagulable disorders, Polycythemia vera, Hepatocellular carcinoma, Protein C and S deficiency, and Pregnancy.

What hemoglobin and hematocrit cutoffs support the diagnosis of Polycythemia vera in men?

Hemoglobin $> 16.5\,\text{g/dL}$ and hematocrit $> 49\%$.

What hemoglobin and hematocrit cutoffs support the diagnosis of Polycythemia vera in women?

Hemoglobin $> 16\,\text{g/dL}$ and hematocrit $> 48\%$.

How does living at higher altitudes affect baseline hematocrit measurements?

Higher altitudes tend to produce higher baseline hematocrit values.

Which optic disc abnormality is demonstrated on the left compared to the normal disc on the right?

Papilledema (optic disc swelling with blurred disk margins).

What mathematical formula represents the 'Rule of Three' connecting Hemoglobin and Hematocrit?

$\text{Hb} \times 3 = \text{Hct} \pm 3$.

In a centrifuged whole blood sample from a normal subject, what percentages are occupied by plasma, formed elements, and the buffy coat?

Plasma occupies $55\%$, formed elements (hematocrit) occupy $45\%$, and the buffy coat occupies $1\%$.

Which two gene mutations are primarily associated with Essential Thrombocythemia?

$JAK2$ or $CALR$ gene mutations.

What acute hematologic malignancy can Essential Thrombocythemia transform into?

Acute Myeloid Leukemia (AML).

What morphological feature defines megakaryocytes in the bone marrow of Essential Thrombocythemia?

Abnormal, giant megakaryocytes with hyperlobulated nuclei.

How do environmental temperatures affect the burning and tingling sensations in the extremities of patients with Essential Thrombocythemia?

The burning and tingling often feel worse with heat and improve with cold.

What severe thrombotic complications can occur in Essential Thrombocythemia?

Blood clots leading to chest pain, myocardial infarction (MI), or stroke.

What histopathologic changes occur in the bone marrow in Primary Myelofibrosis?

Granulocytic and megakaryocytic proliferation accompanied by a gradual increase in bone marrow reticulin and collagen fibrosis.

What are the anatomical sites and clinical consequences of extramedullary hematopoiesis in Primary Myelofibrosis?

Extramedullary hematopoiesis occurs in the spleen (causing splenomegaly) and the liver (causing portal hypertension).

What is leukoerythroblastosis?

The abnormal presence of immature granulocytes and normoblasts (nucleated red cells) in the peripheral blood.

What characteristic red blood cell morphology is indicated on this peripheral blood smear?

Dacrocytes (teardrop erythrocytes).

What is the single most common genetic mutation identified in Primary Myelofibrosis?

$JAK2$.

What pediatric demographic is predominantly affected by Kawasaki disease?

Children younger than 5 years of age, with boys affected more frequently than girls.

What core clinical duration of fever is required to establish the diagnosis of Kawasaki disease?

A fever lasting for at least $5\,\text{days}$.

What critical cardiovascular lesion can develop from blood vessel inflammation in Kawasaki disease?

Coronary artery aneurysms, which pose a high risk for thrombosis.

List five principal clinical signs of Kawasaki disease shown in this infographic.

Red, irritated eyes (conjunctivitis); red, cracked lips and strawberry tongue; swollen cervical lymph nodes; polymorphous rash; and redness/swelling/peeling of hands and feet.

Against which specific platelet membrane glycoproteins are IgG antibodies most often directed in ITP?

Glycoproteins IIb-IIIa or Ib-IX (in approximately $80\%$ of patients).

What patient population does acute ITP typically affect, and what event precedes it in $75\%$ of cases?

Children; in $75\%$ of cases, it follows vaccination or a viral infection such as chickenpox or infectious mononucleosis.

What immunologic mechanism triggers autoantibody production against platelets in acute post-viral ITP?

Molecular mimicry between viral antigens and platelet surface antigens.

What percentage of pediatric acute ITP cases fail to spontaneously remit and progress to chronic ITP?

$10-20\%$.

What patient demographic is classically affected by chronic ITP?

Adults, most commonly women under $40\,\text{years}$ of age (female to male ratio of $3:1$).

What are the characteristic findings on a peripheral blood smear in chronic ITP?

Marked thrombocytopenia accompanied by giant platelets.

How do antiplatelet autoantibodies mediate platelet destruction in ITP?

They coat platelets to act as opsonins, promoting recognition and phagocytosis by tissue macrophages in the spleen.

What does a bone marrow biopsy typically reveal in a patient with ITP?

An increased number of normal-appearing megakaryocytes arranged in loose clusters.

What is 'wet purpura', and what is its clinical significance in ITP?

Blood blisters inside the oral mucous membranes; it serves as a clinical harbinger of impending, life-threatening intracranial or internal bleeding.

What is the standard first-line corticosteroid dosing regimen for ITP?

Prednisone at a dose of $1\,\text{mg/kg}$.

Name two thrombopoietin (TPO) receptor agonists used in ITP and their respective routes of administration.

Romiplostim (administered subcutaneously) and Eltrombopag (administered orally).

What target antigen does Rituximab bind when used in refractory ITP?

CD20 on B cells.

What clinical thrombotic and obstetric complications define Antiphospholipid Syndrome (APS)?

Venous and arterial thromboembolism, alongside pregnancy complications such as recurrent miscarriage, stillbirth, or pre-eclampsia.

Which three major antibodies are included in the laboratory evaluation of Antiphospholipid Syndrome?

Lupus anticoagulant, Anticardiolipin antibodies, and Anti-Beta 2 glycoprotein-I antibodies.

What two mechanisms produce thrombocytopenia in patients with Systemic Lupus Erythematosus (SLE)?

Excess immune-mediated platelet destruction and reduced platelet production from megakaryocytes.

What classic dermatologic sign of SLE is depicted on this patient's face?

Malar rash (butterfly rash across the bridge of the nose and cheeks).

How is Evans syndrome defined?

An autoimmune condition defined by the coexistence of two or more cytopenias: autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP), with or without immune neutropenia.

What are the hallmark exocrine gland dysfunctions and autoantibodies associated with Sjogren's syndrome?

Diminished lacrimal and salivary function (xerostomia, keratoconjunctivitis sicca), parotid gland enlargement, and Anti-Ro (SS-A) and Anti-La (SS-B) antibodies.

What is the typical timeframe and immunologic mechanism of Post-Transfusion Purpura?

Profound thrombocytopenia occurring within 2 weeks of transfusion due to alloimmunization against foreign platelet antigens.

What diagnostic cytoplasmic structure is indicated by the arrow in this Acute Myeloid Leukemia (AML) blast?

An Auer rod.

What is the defining pathophysiology of aplastic anemia?

Pancytopenia resulting from hematopoietic stem cell failure in the bone marrow via immune-mediated and intrinsic mechanisms.

What characteristic histopathological changes are seen in this bone marrow core biopsy from a patient with aplastic anemia?

Fatty replacement of lacunar spaces with a marked paucity of nucleated hematopoietic cells, leaving mostly adipocytes and occasional plasma cells.

What symptoms correlate with each cytopenia in the clinical presentation of aplastic anemia?

Anemia causes pallor, tachycardia, and dyspnea; neutropenia causes fever and infections; thrombocytopenia causes petechiae, bruising, and mucosal bleeding.

What survival rate can be achieved in aplastic anemia with hematopoietic stem cell transplantation (HSCT) or triple immunosuppressive therapy (IST)?

Survival rates exceeding $80\%$.

What is myelodysplasia (myelodysplastic syndrome)?

A bone marrow disorder in which blood cell precursors fail to mature properly, resulting in ineffective hematopoiesis and cytopenias.

For which two enzymes does Vitamin B12 act as an essential cofactor during platelet synthesis?

Methionine synthase and methylmalonyl-CoA mutase.

According to the methionine synthase reaction diagram, what substrate is converted to methionine in a Vitamin B12-dependent manner?

Homocysteine.

By which three mechanisms does chronic alcoholism cause thrombocytopenia?

Splenomegaly, folate deficiency, and a direct toxic effect on platelet production, survival time, and function.

How soon after complete abstinence from alcohol does the platelet count begin to recover?

After $2\,\text{to}\,5\,\text{days}$.

How do prosthetic heart valves induce thrombocytopenia?

Post-implantation endothelial damage, shear stress injury, and inflammation trigger platelet consumption at the valve interface.

What is the most common hereditary thrombocytopenia, and what is its mode of inheritance?

$MYH9$-related disease ($MYH9$-RD), inherited in an autosomal dominant (AD) pattern.

What is the classic hematologic triad present from birth in $MYH9$-related disease?

Platelet macrocytosis ($> 40\%$ of platelets $> 3.9\,\mu\text{m}$ in diameter), thrombocytopenia ($< 150 \times 10^9/\text{L}$), and Döhle-like leukocyte inclusions.

What are Döhle-like bodies in May-Hegglin anomaly / $MYH9$-RD?

Cytoplasmic aggregates of $MYH9$ protein forming light blue, sharply defined crescent or round inclusion bodies inside neutrophil granulocytes.