thrombocytopenia

Question 1

causes of theombocytopenia

Answer 1

A. Decreased Platelet Production (Bone Marrow Problems)
• Bone marrow suppression (chemotherapy, radiation)
• Aplastic anemia (bone marrow failure)
• Leukemia or other cancers affecting the bone marrow
• Viral infections (HIV, hepatitis, EBV)
• Vitamin deficiencies (B12, folate)

B. Increased Platelet Destruction or Consumption
• Immune causes:
• Immune Thrombocytopenic Purpura (ITP) → Autoimmune destruction of platelets
• Lupus or other autoimmune diseases
• Non-immune causes:
• Disseminated Intravascular Coagulation (DIC) → Platelets consumed in widespread clotting
• Thrombotic Thrombocytopenic Purpura (TTP) → Small clot formation consuming platelets
• Hemolytic Uremic Syndrome (HUS) → Often seen in E. coli infections

C. Increased Platelet Sequestration (Trapped in Spleen)
• Liver disease → Leads to an enlarged spleen (splenomegaly), which traps platelets
• Portal hypertension (from cirrhosis)

Question 2

symotoms of thrombocytopenia

Answer 2

• Mild cases may have no symptoms.
• Easy bruising (ecchymosis)
• Petechiae (tiny red or purple spots on skin due to bleeding under the skin)
• Prolonged bleeding from cuts or injuries
• Nosebleeds (epistaxis) or bleeding gums
• Heavy menstrual bleeding
• In severe cases: Spontaneous internal bleeding, including brain hemorrhage

Question 3

IIMMUNE THROMBOCYTOPENIC PURPURA (ITP)

Answer 3

Autoimmune destrucAon of platelets and inhibiAon of megakaryocyte producAon
• Abnormal T-cells & B-cells to produce IgG anAbodies are formed against platelets.
• PLT-AB complex is destroyed by spleen
• Common cause of isolated thrombocytopenia but it a diagnosis of exclusion
• Auto-Abs mediated inhibiAon of megakaryopoiesis

Question 4

ITP

Answer 4

immune mediated where ur body produces antibodies againts ur own platelets

Question 5

clinical presentation of ITP

Answer 5

• Children: acute onset of purpura following viral infecAon, usually self-limiAng 80% of cases resolve spontaneously within 6 months
• Adult: usually in young women (20 to 40 years of age), may occur with other autoimmune dx: SLE and thyroid disease, In paAents with lymphoma and leukemia
. • Patients may have minor mucocutaneous bleeding, easy bruising, petechiae, epistaxis, menorrhagia, hematuria, GI bleeding

Question 6

there are two types of ITP acute and chronic

Answer 6

1. Acute ITP:
   • More common in children
   • Often follows a viral infection (e.g., flu, chickenpox)
   • Usually self-limited and resolves within weeks to months
2. Chronic ITP:
   • More common in adults (especially women under 40)
   • Persists for more than 6 months
   • Requires long-term management

Question 7

diagnosis of ITP

Answer 7

• Isolated thrombocytopenia <100,000/µL
• Bone marrow aspiraAon shows increased megakaryocytes (usually not indicated)
• Peripheral smear with megakaryocytes and no other abnormaliAes, reveals decreased platelets
• RBC, PT, PTT & Fibrinogen all are normal

Question 8

tx of ITP when to treat

Answer 8

Platelet count >30,000/µL and no bleeding → Observation only
• Platelet count <30,000/µL or active bleeding → Treatment needed

Question 9

tx of ITP

Answer 9

o CorAcosteroids

o IVIG (IV immune globulin),

o Splenectomy = if the paAent is not responding to steroids and IVIG (induces remission in 70% to 80% of the cases of chronic, steroid-resistant ITP)

o Rituximab + thrombopoieAn receptor agonist “e.g.,eltrombopag” (increases producAon of platelets) may be used in refractory ITP

Question 10

bernard soulier syndrome

Answer 10

Autosomal recessive disorder of platelet adhesion (to sub endothelium) due to absent platelet glycoprotein 1b- IX-V, which acts as a receptor for von Willebrand factor.

• caused by mutations in one of three genes: GP1BA, GP1BB, or GP9

Question 11

TTP

Answer 11

• Deficiency in vW Factor cleaving enzyme called ADAMTS-13
• Patents lack functional ADAMTS13, a proteas that cleaves von willebrand factor (vWf)
• Resulting in abnormal large vWF that aggregate platelets and lead to microvascular thrombosis and thrombocytopenia (low PLT)

Question 12

the terrible pentad in TTP

Answer 12

1. Microangiopathic Hemolytic Anemia (MAHA)
   • Destruction of red blood cells (schistocytes on blood smear)
   • Leads to anemia, jaundice, fatigue
2. Thrombocytopenia (Low Platelets)
   • Due to platelet consumption in microthrombi
   • Causes petechiae, purpura, and bleeding
3. Neurologic Symptoms
   • Confusion, headaches, seizures, stroke-like symptoms
   • Due to small vessel occlusion in the brain
4. Fever
   • Less common but may be present in acute episodes
5. Renal Failure
   • Hematuria, proteinuria, elevated creatinine
   • Due to microthrombi affecting kidney circulation

Question 13

hemolytic uremic syndrome

Answer 13

• Can present similarly to TTP
• Clinical syndrome characterized by progressive renal failure that is associated with microangiopathic
(nonimmune, Coombs-nega.ve) hemoly.c anemia and thrombocytopenia.
• Most common cause of acute kidney injury in children
• Usually following infec.on with E. coli O157:H7 and shigella (shigella-like toxin)
• Usually resolves spontaneously.
• If severe, will need plasma exchange, and if not available FFP infusion

Question 14

what is main diff btwn TTP and HUS

Answer 14

TTP - common is encephalopathy
HUS- renal failure more common

Question 15

evans syndrome

Answer 15

is a rare autoimmune disorder where the immune system mistakenly attacks both red blood cells (RBCs) and platelets, leading to a combination of:
1. Autoimmune Hemolytic Anemia (AIHA) → Destruction of RBCs → Anemia, jaundice
2. Immune Thrombocytopenia (ITP) → Destruction of platelets → Increased bleeding risk
3. (Sometimes) Autoimmune Neutropenia → Destruction of white blood cells (WBCs) → Increased infections

Question 16

DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

Answer 16

widespread clotting occurs throughout the body, leading to both excessive clot formation and severe bleeding due to platelet and coagulation factor consumption.

Question 17

causes of DIC

Answer 17

(Mnemonic: STOP Making New Thrombi)
• Sepsis (most common, especially Gram-negative bacteria)
• Trauma (severe burns, crush injuries, head injury)
• Obstetric complications (abruptio placentae, amniotic fluid embolism)
• Pancreatitis (acute)
• Malignancies (leukemia, metastatic cancer, APL)
• Nephrotic syndrome (less common)
• Transfusion reactions or severe hemolysis

Question 18

what is hemophilia

Answer 18

A hereditary blood disorder occurring almost exclusively in males that is marked by delayed clotting of the blood

X linked recessive: mother passes a copy of the defective gene to a male child

Question 19

if a female is a carrier of hemophilia and male diseased

Answer 19

Female carrier > 50% of sons are affected, 50% of daughters are carriers
•Male diseased > all sons are normal, all daughters are carriers

Question 20

hemophilia A

Answer 20

-defeciency in factor 8
- Desmopressin (synthetic vasopressin) may be used for some patients with mild hemophilia to raise the level of factor VIII.

Question 21

hemophilia B

Answer 21

defeciency in factor 9

Question 22

VON WILLIBRAND DISEASE:

Answer 22

Von Willebrand Disease (vWD) is the most common inherited bleeding disorder, caused by a deficiency or dysfunction of von Willebrand Factor (vWF), which is essential for platelet adhesion and Factor VIII stabilization.

Question 23

thrombophilia

Answer 23

Hypercoagulability (also called thrombophilia) refers to a condition where the blood has an increased tendency to form clots (thrombosis). This can lead to abnormal clot formation in veins or arteries, increasing the risk of deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, or heart attack.

Question 24

Inherited Causes of Thrombosis (Inherited Thrombophilia)

Answer 24

• Caused by a genetic defect
• Deficiency of natural anticoagulant
• Mutation in a coagulation factor (resistance to inhibition)

Question 25

Who to workup for hypercoagulability:

Answer 25

• Pts with recurrent or multiple thrombosis or thrombosis at unusual sites ex: cerebral/mesenteric/portal veins (only if it will change management plan) • Pts with warfarin-induced skin necrosis or neonatal purpura fulminans • Thrombosis in young age (<45) or without predisposing factors

Question 26

protein C defeciency

Answer 26

Protein C is a natural anticoagulant that degrades Factor Va and Factor VIIIa. • A deficiency in Protein C results in reduced inactivation of clotting factors, leading to prolonged clotting activation

Question 27

protein S

Answer 27

• Protein S serves as a cofactor for Protein C, enhancing its anticoagulant activity. • A deficiency in Protein S results in impaired activation of Protein C, further increasing thrombin production and clot formation.

Question 28

Prothrombin Gene Mutation (PT) G20210A

Answer 28

• A mutation in the prothrombin gene results in increased levels of prothrombin (Factor II). • This leads to excess thrombin production, promoting excessive clot formation.

Question 29

Activated Protein C Resistance (Factor V Leiden):

Answer 29

• Mutation in Factor V gene leads to resistance to Protein C. • Protein C normally inactivates Factor V, but in Factor V Leiden, Factor V cannot be inactivated efficiently. • This results in increased thrombin generation, leading to hypercoagulability.

Question 30

Antithrombin III Deficiency

Answer 30

• Antithrombin III inhibits thrombin and Factor Xa, which are essential for clot formation. • A deficiency in Antithrombin III leads to ineffective inhibition of thrombin, promoting abnormal clotting.

Question 31

anaphylactic shock

Answer 31

• Rapid onset of shock, angioedema/urticaria, & respiratory distress • Occurs within seconds to minutes of transfusion • Mechanism: type I hypersensiAvity reaction to donor plasma proteins (due to preformed recipient anAbodies) • Caused by recipient anti IgA anAbodies (IgA deficient individuals)

Question 32

managemnt of anaphylactic shock

Answer 32

o Immediate cessation of transfusion Intramuscular epinephrine o Hemodynamic and respiratory support (vasopressors and mechanical ventilation) o Antihistamines and glucocorticoids

Question 33

Acute hemolytic reaction:

Answer 33

• Medical emergency • Fever, flank pain, hemoglobinuria, renal failure (due to immune complex deposiAons), & DIC Within 1 hr of transfusion • Positive direct Coombs test • Pink plasmin (plasma free hemoglobin >=25mg/dL)

Question 34

what causes acute hemolytic reaction

Answer 34

An acute hemolytic transfusion reaction is a serious, potentially life-threatening reaction that occurs when red blood cells (RBCs) from a blood transfusion are attacked by the recipient’s immune system. This leads to rapid destruction (hemolysis) of the transfused red blood cells, causing a cascade of complications.

Question 35

Febrile non-hemolytic reaction

Answer 35

FNHTR is caused by two main mechanisms: 1. Cytokine Release from White Blood Cells (WBCs) • Stored blood products contain WBCs that break down over time, releasing inflammatory cytokines (e.g., IL-1, IL-6, TNF-α) into the plasma. • When transfused, these cytokines stimulate the hypothalamus, leading to fever and chills. • This is more common in platelet transfusions since platelets are stored at room temperature, allowing more cytokine buildup. 2. Recipient’s Immune Response Against Donor WBCs • The recipient’s preformed antibodies react with donor leukocytes in the transfused blood. • This immune response triggers the release of pyrogens, causing fever and mild inflammation.

Question 36

Transfusion related acute lung injury:

Answer 36

Respiratory distress, fever & hypotension, and signs noncardiogenic pulmonary edema within 6 hours of transfusion. • Caused by donor anti leukocyte antibodies

Question 37

Urticaria/allergic reaction:

Answer 37

Urticaria, flushing, angioedema, and pruritis Within 2-3hrs of transfusion • Caused by recipient IgE antibodies and mast cell activation • Mechanism: allergic reaction to components in donor plasma (due to preformed recipient antibodies)

Question 38

primary hypotension reaction

Answer 38

Transient hypotension often in patients taking ACEI within minutes of transfusion caused by bradykinin in blood products (normally degraded by angiotensin-converAng enzyme)

Question 39

vitamin K defeciency usually from what

Answer 39

Obtained K exogenously from intestinal absorption of dietary Vit. K (leafy green vegetables) and endogenously from bacterial production of Vit. K in intesAne. • Deficiency is most commonly due to inadequate intake, intestinal malabsorption (e.g.,small bowel disease, inflammatory bowel disease, obstructive jaundice), or hepatocellular disease

Question 40

in VIT k defeciency what would be the problem in coagulation

Answer 40

decreased plasma levels of all the prothrombin complex proteins (factors 2,7,9,10, and protein C and S, as it serves as a key cofactor in posttranslational modification (γ-carboxylaAon)--> initial increase of PT, followed by prolongation of APPT

Question 41

To diagnose suspected DVT =DVT Well’s score:

Answer 41

Wells Score for DVT – Mnemonic: “C3PO R2D2” Cancer (active malignancy) 1 Calves swollen (>3 cm compared to the other leg 1 Collateral superficial veins (non-varicose) 1 Pitting edema (confined to symptomatic leg) 1 Other diagnosis less likely than DVT 1 Recent immobilization (bedridden >3 days or major surgery within 4 weeks) 1 Recent history of DVT/PE 1 DVT localized tenderness 1 Doc’s (physician’s) judgment: Strong suspicion of DVT 1

Question 42

to diagnose suspected PE wells score

Answer 42

“Don’t Die, Tell The Team To Calculate Criteria!” DVT signs & symptoms (leg swelling, pain) 3 Diagnosis of PE is more likely than other causes 3 Tachycardia (HR >100 bpm) 1.5 Three days of immobilization/surgery in past 4 weeks 1.5 Thromboembolism history (previous DVT/PE) 1.5 Coughing up blood (hemoptysis) 1 Cancer (active or treated within 6 months) 1

Question 43

HEPARIN INDUCED THROMBOCYTOPENIA (HIT)

Answer 43

1.Heparin and platelet factor 4 (PF4) form a complex → producAon of IgG anAbodies against the heparin/PF4 complex → IgG anAbody-heparin/PF4 immunocomplex binds on platelet surface → platelet acAvaAon and aggregaAon → consumpAon of platelets (thrombocytopenia) and arterial/venous thrombosis 2.Thrombocytopenia also occurs due to phagocytosis of IgG anAbody-heparin/PF4 immunocomplex-bound platelets by macrophages in the spleen, liver, and bone marrow.

Question 44

HIT type 1

Answer 44

• Occurs within 1-2 days of heparin exposure. • Caused by direct platelet activation by heparin. • Platelet count normalizes despite continued heparin use. • No clinical significance → No treatment needed.

Question 45

HIT type 2

Answer 45

• Occurs 5-10 days after heparin exposure (or sooner if previously exposed). • Caused by IgG antibodies against platelet factor 4 (PF4)-heparin complex. • Activates platelets, causing thrombocytopenia and thrombosis. • Life-threatening risk of arterial and venous clots → Requires immediate intervention.

Question 46

how big is the fall in platelets in HIT

Answer 46

• Thrombocytopenia (platelets drop >50% from baseline).

Question 47

warfarin induced skin necrosis

Answer 47

1. Warfarin inhibits vitamin K-dependent clotting factors (II, VII, IX, X) AND anticoagulant proteins C & S. 2. Protein C has a shorter half-life (6-8 hours) than Factor II (prothrombin) and Factor X (longer half-lives). 3. In the first few days, Protein C levels drop faster than pro-coagulant factors, creating a temporary pro-thrombotic state. 4. Microvascular thrombosis occurs in the dermis, leading to ischemia and necrosis of the skin.