Lecture 1 (hem/onc)-Exam 1 Flashcards
What is hematology?
The medical specialty that pertains to the anatomy, physiology, pathology, symptomatology, and therapeutics related to blood and blood forming organs
What is the typical blood volume? What is the breakdown?
Blood volume is typically ~5L = 2L cellular/solid + 3L plasma/liquid
- What is in the plasma?
- What is the type of blood cells?
- Plasma is mostly water, but also contains proteins, coagulation factors, electrolytes, hormones, and carbon dioxide
- Types of blood cells: erythrocytes, leukocytes, & thrombocytes
Platelets are in circulation for how long? RBCs?
Platelets are in circulation for 7-10 days, RBCs for 120 days, and WBCs vary by type
- What is left shift?
- What is the FIRST cell to differenant into all WBC/RBC?
- An increase in WBC accompanied by a specific increase in neutrophils especially immature neutrophils
- Multipotent uncommunited stem cell
What is a peripheral blood smear? What does it look at?
- To qualify blood cells, peripheral blood smear or bone marrow biopsy is obtained
- Size, shape, and distribution of cells are observed
What are these?
- Top: Peripheral Blood Smear (Wright stain)
- Bottom: Bone Marrow Core Biopsy (H&E stain)
Where do you do a bone marrow biopsy?
PSIS placement
What happens to hgb/hct in with men and pregnant people?
- Hgb/HCT higher in men than in women of child-bearing age-> testerone because increase EPO
- Hgb/HCT and platelet count both naturally decrease during pregnancy (increase dependence)
What type of wbc cells are higher in children and adults?
- Children: increase lymphocytes
- Adults: increase neutrophils
What are euvolemic baseline?
What is a hemodilute sample? How do you fix it?
- Hypervolemia (increase volume), ie if same patient has an acute heart failure exacerbation (water excess)
- Dialysis will cause the volume to go back to normal
NO BLOOD DISORDER
What is a hemoconcentrated sample? How do you fix it?
- Hypovolemia, ie if same patient is severely dehydrated (water deficient)
- Hydrate patient
NO BLOOD DISORDER
- How is a CBC helpful?
- What are three possibilities with cytopenias?
Medical terminology: “Cyto”-”penia”= cell lacking/deficiency, ie thrombocytopenia .
“Cy”-”tosis” = cell increase (also means affected by), ie erythrocytosis.
“-philia”= love for (ie neutrophilia)
What does WBC differential include?
Quantitates different types of white blood cells in the peripheral blood including neutrophils, eosinophils, lymphocytes, monocytes, basophils, and abnormal leukocytes (if present)
What are neutrophils? (what else can be called)
Neutrophils= bands+ segmented; also called polymorphonuclear neutrophils (PMNs,) polymorphonuclear leukocytes (PMLs), or granulocytes
What is the definition of leukopenia?
Definition: WBC count less than 4.5 billion cells/L (4,500/mm³)
What are the causes of leukopenia? (8)
- Medications (including chemotherapy, anti-thyroid medications, & some antibiotics, ie linezolid)
- Infections: viral (ie HIV, hepatitis A/B/C, EBV, CMV, HHV6), bacterial (ie mycobacterial, Lyme, malaria, salmonella), & fungal
- Malignancies: leukemias, lymphomas, myelodysplastic syndromes
- Aplastic anemia
- Autoimmune disorders
- Radiation exposure
- Alcohol abuse disorder
- Vitamin/mineral deficiencies (B12, copper)
- What is leukocyosis?
- What lab is helpful?
- Definition: WBC count greater than 11 billion cells/L (11,000/mm3)
- In this case, WBC differential is especially helpful!
causes of leukocytosis
What causes high neutophiles, eosinophils, and basophils?
- Neutrophils high: infection (“left shift” ≥ 10% neutrophil bands), inflammation, steroid effect, CML
- Eosinophils high : hypersensitivity reaction, parasitic infections, lymphomas (Hodgkin’s), myeloid leukemias
- Basophils high : hypersensitivity reaction, CML
What causes high monocytes, blasts, lymphocytes, atypical lymphocytes?
- Monocytes high : viral infections (ie EBV, CMV), bacterial infections
- Blasts high : acute leukemias, myelofibrosis
- Lymphocytes high: EBV infection, Bordetella pertussis, CLL
- “Atypical” lymphocytes high: infection, inflammatory response, lymphomas
What is hemochromatosis? What are the risk factors?
- iron overload
- Risk factors: severe hemoglobinopathies, hematological malignancies, sideroblastic anemias, & multiple RBC transfusions
RBC transfusions has a lot of iron in it
What are the sx of hemochromatosis? What are the labs and imaging done?
- Signs/symptoms: lethargy, hepatomegaly, hepatic cirrhosis, arthropathy/arthritis, diabetes mellitus, heart disease, hypogonadism (depends on where is desposits)
- Labs: serum ferritin level significantly elevated, transferrin saturation elevated, and liver enzymes elevated
- Imaging/diagnostics: MRI/MRE of liver and liver biopsy
What is the txt of hemochromatosis?
iron chelation agents (ie IV deferoxamine or PO deferasirox) & supportive treatment of damaged organs
What does this show of a pt with many blood transfusion?
Hereditary hemochromatosis:
* What type of form?
* What is it due to?
* What is the normal age and gender?
- Inherited form of iron overload
- Due to mutation in HFE gene on chromosome 6; predominant in those of Northern European descent (res disorder)
- Usually asymptomatic until age 40-60 years
- Men > women
Hereditary hemochromatosis:
* What are the sxs?
* What is the txt?
- Same signs/symptoms (except bronze skin-> iron in skin+melanin production), lab findings, & radiological findings as acquired form of hemochromatosis
- Increase ferritin and liver enzymes
- Treatment: therapeutic phlebotomy
Regulation of the Clotting Cascade
What are three ways that the body prevents a clot from becoming a thrombus?
- Blood flow: dilutes and washes away any clotting factors that get activated (so it does not go overboard)
- Normal levels of protein C, protein S, antithrombin, & tissue factor pathway inhibitor
- Fibrinolytic system: breaks down the clot once it’s formed
If one of these fail, you can a clot
Thrombosis:
* The obstruction of blood flow due to what?
* Results in what?
* How many people are affected by Venous thromboembolism?
* What is the number one cause of dealth in the US?
* What is the 5th leading casue of death in the US?
- The obstruction of blood flow due to formation of clot (thrombus)
- Results in tissue anoxia & damage
- As many as 900,000 people affected by venous thromboembolism in the U.S. each year & 60,000-100,000 die as a result
- Coronary heart disease remains the number one cause of death in the U.S.
- Cerebral vascular disease remained the 5th leading cause of death in the U.S. as of 2020
Arterial thrombus:
* Due to what?
* What type of clot?
* Occurs where?
Venous thrombus:
* Due to what?
* What type of clot?
* Occurs where?
Explain how an arterial and venous thrombosis comes about in the vessels
* What do you give to tx?
What is the virchows’s triad?
- Stasis of blood flow: immobilization, bed rest, extended travel
- Endothelial injury: trauma, surgery
- Hypercoagulability: imbalance of protein in blood
What are the hypercoagulable states we need to know?
- Pregnancy and postpartum
- Smoking
- surgery
- estrogen use (birth control and hormone replacement)
- Cancer (active)
Malignancy as a hypercoag state:
* how does that happen?
* What is it associated with?
* What do 20% of patients have?
- Due to the production of substances with procoagulant activity, such as tissue factor and cancer procoagulant
- Associated with both solid tumor and blood cancers
- ~20% of patients with symptomatic DVT have a known active malignancy
What is trousseau syndrome?
a cancer-associated migratory thrombophlebitis(superifical blood clot
Intra- and Post-Operative Period as a endothelial injury:
* What is the cause?
* When does risk increase?
* What surgeries are at higher risk?
- Due to tissue injury & additive effects of anesthesia, pain, hypothermia, bleeding and fasting->lead to increases in cytokines, factor VIII, vWF, fibrinogen, platelet count & reactivity
- Risk increases with more invasive and longer procedures
- > 50% risk with some orthopedic (hip+knee replacement) & cardiothoracic surgeries (open chest)-> give preventive anticog thearpy
Pregnancy or Exogenous Estrogen as a hypercoag state:
* Assoicated with what?
* Symptoms may overlap with what?
- Associated with progressive increases in several coagulation factors, including factors I, II, VII, VIII, IX, and X, along with a decrease in protein S
- Symptoms may overlap those of pregnancy (leg or abdominal swelling, shortness of breath), delaying diagnosis
Antiphospholipid Syndrome
* What type of disorder?
* Disagnosed by what?
* What clot is possible?
* What are the pregancy complications?
* What is present in 25% of patients?
- Autoimmune disorder (ex lupus)
- Diagnosed by antibody testing: immunoassays for cardiolipin, beta2-glycoprotein (GP) I, and lupus anticoagulant (LA) phenomenon
- Arterial thromboses possible
- Pregnancy complications: fetal loss, placental insufficiency, preeclampsia
- Thrombocytopenia present in ~25% of patients with APS
Thrombocytosis
* What is the definition?
* 90% of cases are what?
* What are other cases due to?
* Possible carries increased risk for what?
- Definition: Platelet count greater than 450,000/µL
- 90% of cases are secondary, also called “reactive”: infection, inflammation (including cancer), iron deficiency, or post-splenectomy
- 10% are due to myeloproliferative disorders
- Possibly carries increased risk for thromboses if >1 million/µL
- Most venous clots are what?
- Where does a PE come from usually?
- Many many risk factors in majority of causes?
- Most venous clots are deep vein thrombosis (DVT) of an extremity or pulmonary embolism (PE)
- PE is usually embolus of lower extremity DVT
- Collectively called venous thromboembolism (VTE)-> both DVT and PE
- ≥ 2 risk factors in majority of cases
Diagnosis of DVT:
* What is present?
* What are the symtoms?
* What are the PE findings?
+Risk factors present (“provoked”)
Symptoms
* Swelling of limb (usually in lower extremity) &/or progressive, constant, unilateral calf pain/cramping
Physical exam findings
* Pitting edema of an extremity (unilateral or unequal), rubor, calor, calf tenderness, superficial venous dilation, positive Homan’s sign (pain in cald when dorsiflex foot)
When can you see upper extremitiy DVT?
lines place: PICC, central line, port
What are the steps to rule in/out DVT?
- Obtain history (hx of DVT) and physical exam- consider Homan’s sign
- Calculate Well’s score
- If appropriate, check D dimer level
- If elevated D dimer level or high clinical suspicion, confirm with ultrasound with venous doppler study of the limb (gold standard)
What is the wells score for DVT?
What are the superifican and deep veins?
What are the physical sx difference btw venous and arterial thrombosis in lower ext?
Diagnosis of PE
* What is present?
* What are the symptoms?
* What are the clinical signs?
+Risk factors present (“provoked”)
Symptoms
* Dyspnea, cough, chest pain (pleuritic), hemoptysis, syncope, shock, sudden cardiac arrest
Clinical signs
* Tachycardia (MOST COMMON), hypoxia (especially with exertion- 6 min walk test), tachypnea, cyanosis, fever, leg swelling (DVT)
What are the steps to rule in/out PE?
- Obtain history and physical exam
- Rule out other medical emergencies (ie EKG, troponin level, chest-ray)
- Calculate Well’s score
- If appropriate, check D dimer level
- If elevated D dimer level or high clinical suspicion, confirm with CT angiogram of the chest (if eGFR <60, substitute with V/Q scan)
What are the possible diagnostic findings with PE? (4)
- Elevated D dimer level
- EKG: Normal vs. Sinus tachycardia vs. S1Q3T3 sign
- Chest x-ray: Usually normal
- Echocardiogram: Normal or signs of RV strain (cor pulmonale)
What is the wells score of PE?
What are the reasons for false positive levels and what are reasons for false negative levels?
What is shown on EKG for PE?
What are these? (think PE)
- Left: Westermark’s sign
- Right: Hampton’s hump
What do these show?
How do clinicans describe PEs?
txt of VTE:
* What is the mainstay theraoy?
* How long is thearpy for smaller and larger vein?
- Anticoagulation is mainstay of therapy
- 3 months for distal (smaller vein) DVT
- 3-6 months for PE, multi-vessel, or proximal DVT (larger vein)
What are the types of Types of “blood thinners”?
What are the diffrent Clotting cascade blockers/ Anticoagulants ?
- Indirect Thrombin inhibitors (heparin, enoxaparin, fondaparinux)
- Direct Thrombin Inhibitors (dabigatran)
- Direct Factor Xa Inhibitors/DOACs (rivaroxaban, apixaban)
- Vitamin K antagonists (warfarin)
4 options depending extent of VTE, patient’s co-morbidities/medications, & availability of reversal agents:
What if your patient on an anticoagulant
now has activebleeding, what is the potential universal reversal agent?
Ciraparantag
What are absolute contraindications to anticoagulation?
- Active bleeding
- Major trauma
- Recent or planned high risk surgery
- Severe bleeding disorder (as with liver failure)
- Intracranial hemorrhage
What are relative contraindications to anticoagulation?
- History of recurrent bleeding from multiple gastrointestinal telangiectasias
- Intracranial or spinal tumors
- Large AAA with concurrent uncontrolled HTN
- Stable aortic dissection
- Recent or planned low risk surgery
- High risk of falling
- Platelet count < 50,000
- INR >1.5
What is the reason for IVC filters?
- If anticoagulation is contraindicated in patient with VTE, consider an Inferior Vena Cava filter
- Prevents emboli to lungs (PE) but causes endovasular injury so can increase risk of DVT but decrease becoming PE
- Temporary
What is the treatment of severe VTE?
- Fibrinolysis (ie IV tissue plasminogen activator)
- Pharmaco-mechanical thrombolysis (catheter-directed)
- Surgical embolectomy
What is the prevention from surgery?
Thrombophlebitis
* What is this?
* present with what?
* What does it not require?
* What may help?
When should you suspect inherited hypercoagulability?
Inherited Hypercoagulability
What is the hypercoagulation workup?
- Leiden factor V mutation (MC)
- Anticardiolipin/antinuclear/antiphospholipid
- Antithrombin III assay
- HIT assay
- Prothrombin 20210A mutation antibodies
- Protein C assay
- Protein S assay
- Lupus anticoagulant
- Fibrinogen level
- Lipid panel
- Thyroid Stimulating Hormone
- Cocaine metabolites
Factor V Leiden
* MC what?
* Results from what?
* What is most likely present?
* Leads to what?
* How do you dx?
- Most common inherited thrombophilia disorder
- Results from a point mutation in the F5 gene, which encodes the factor V protein in the coagulation cascade
- Family history likely present
- Leads to protein C resistance (leads to DVT and PEs
- Diagnosed by gene testing for mutation (arterial thrombi common)
Protein C & S Deficiencies
* May occur?
* What type of gene mutations?
* What also exists?
* Dx by?
- May occur concomitantly or alone
- PROS or PROC gene mutations
- Acquired forms also exists
- Diagnosed by combination of quantitative and functional assays
Antithrombin III Deficiency
* Common or rare?
* What is there an increase risk of?
* Dx via what?
* If heparin must be administered (ie CV surgery), may give what?
Summary page:
* Both arterial and venous thromboses are a major cause of what?
* Venous thromboses are due to what (3)
* Hypercoagulable states include what? (4)
* DVT presents with what?
* PE presents with what?
* VTE require what txt?
* Multiple VTE with no clear hypercoagulable state should trigger a workup for what?
Hemostasis
What does vascular injury lead to? (4 steps)
* How longs does it take for the first 3 steps?
Explain the process of primary hemostasis
Adhesion, Aggregation/Activation, & Stabilization
* Primary hemostasis is when your body forms a temporary plug to seal an injury. To accomplish that, platelets that circulate in your blood stick to the damaged tissue and activate. That activation means they can “recruit” more platelets to form a platelet “plug” to stop blood loss from the damaged area
Explain the process of secondary hemostasis
Coagulation Cascade
* Secondary hemostasis refers to the deposition of insoluble fibrin, which is generated by the proteolytic coagulation cascade. This insoluble fibrin forms a mesh that is incorporated into and around the platelet plug. This mesh serves to strengthen and stabilize the blood clot.
What is the more modern view of coagulation?
More modern view of coagulation:
1. Initiation phase
2. Amplification phase
3. Propagation phase
4. Stabilization
Explain the process of fibroinolysis
Fibrin clot degradation
* Fibrinolysis is the degradation of the fibrin network of a blood clot. Fibrinolysis is required to achieve hemostatic balance. Fibrinolysis can occur naturally in the body or with delivery of pharmacological agents. Rate of fibrinolysis is affected by the fibrin structure and the clot’s cellular components.
What do you ask for the hisory of bleeding patient?
What are the Signs of primary hemostatic dysfunction
(platelet disorder)?
What are the Signs of secondary hemostatic dysfunction
(clotting factor disorder)?
What does this show?
Signs of primary hemostatic dysfunction
(platelet disorder)
What does this show?
Signs of secondary hemostatic dysfunction
(clotting factor disorder)
What are the initial workup for labs in a bleeding patient?
- CBC
- “Coags”:
* aPTT, partial thromboplastin time, tests intrinsic pathway, normal range: 25-40 sec
* PT, prothrombin time, tests extrinsic pathway, normal range 11-15 sec
* INR, international normalized ratio, normal value 1.0
+/- 3. Thromboelastogram (TEG)-> surgery setting
What are the coag tests and what do they test?
- aPTT, partial thromboplastin time, tests intrinsic pathway, normal range: 25-40 sec
- PT, prothrombin time, tests extrinsic pathway, normal range 11-15 sec
- INR, international normalized ratio, normal value 1.0
What is TEG?
TEG is a non-invasive test that quantitatively measures the ability of whole blood to form a clot. The principle of this in vitro test is todetect and quantify dynamic changes of the viscoelastic properties of a blood sample during clotting under low shear stress.
What is the second tier Workup in Bleeding Patient
What does thrombin time test?
Thrombin time, TT/TCT (thrombin clotting time: tests common pathway, along with fibrin split products)
What is thrombocytopenia?
* What is normal platelet count?
* What is clinically significant?
* What is there a risk if under 50K and 10K?
What are the causes of decreased platelet production?
What are the causes of increased platelet consumption?
thrombocytopenia
What is the cause of sequestration/other?
What are the causes of thrombocytopenia?
Thrombocytopenia due to Systemic Disorders (7)
What are drug induced thrombocytopenias?
Heparin Induced Thrombocytopenia (HIT)
* Occurs when?
* What is due to?
* What is the 4 Ts?
* How is it confirmed?
- Occurs within 5-14 days of exposure to unfractionated heparin or, less likely, LMWH
- Due to antibodies made against platelet factor 4 (PF4); reduce number and activate platelets
- 4 T’s score to assess probability of HIT (Thrombocytopenia, Timing relative to heparin exposure, presence of Thrombosis, and oTher causes for thrombocytopenia)
- Confirmed by ELISA or functional assays (takes time so that is why the 4 T were made)
What is the txt of heparin induced thrombocytopenia (HIT)
Management: stop heparin & avoid future exposures, venous dopplers of bilateral lower extremities, & start a non-heparin anticoagulant (ie argatroban, fondaparinux) -> because clots
Immune/Idiopathic Thrombocytopenic Purpura (ITP)
* What type of disorder?
* Affects who?
* Sx of what?
* What are the labs?
* How do you dx?
- Autoimmune disorder with IgG antibodies against platelets
- Affects both children and adults
- Signs/symptoms of thrombocytopenia-> mild bleeding
- Laboratory exams: Platelet count <50k (low), no anemia or leukopenia (cells are good) , enlarged platelets on peripheral smear, normal coagulation studies (always check coag). Platelet-associated IgG antibody assay available
- Diagnosis of exclusion
F>M, chlidren with viral or adults in 20-50yo
ITP txt:
* Required when?
* What is first line?
* What is second line?
- Required only when platelets <30k or excessive bleeding
- First line therapy: Corticosteroids, IVIG, Anti-RhoD or RhoGAM® if Rh+, transfusions if bleeding
- Second line therapy: thrombopoietin receptor agonists, rituximab, fostamatinib, splenectomy for relapses
Thrombotic Thrombocytopenic Purpura/ Hemolytic Uremic Syndrome (TTP/HUS)
* What is this due to?
* HUS may be associated with what?
* Why is it a medical emergency?
- Microangiopathy due to antibodies to ADAMTS13, pregnancy, malignancy, HIV, drugs (quinine), or infection
- HUS may be associated with E. coli O157:H7 or Shiga toxin, especially in children
- Medical emergency due to ischemic multi-organ failure
LOOKS SICK UNLIKE ITP
What is the pentad ttp/hus?
TTP/HUS:
* What are the labs/diagnostics?
* What are the txt?
- Labs/Diagnostics: low platelet count, normal PT and PTT, elevated creatinine & BUN, hemolysis*, ADAMTS13 assay (indicates TTP over HUS)
- Treatments: emergent plasma exchange if TTP >HUS, eculizumab if HUS>TTP, RBC transfusions, hemodialysis, IVIG, corticosteroids, rituximab, cyclophosphamide, splenectomy
*low hgb/hct, schistocytes on peripheral smear, elevated reticulocytes, elevated LDH, elevated indirect bilirubin, hemoglobinuria
Hemolysis, Elevated Liver enzymes, and Low Platelet (HELLP) Syndrome
* What type of disorder?
* What do the labs show?
* What is there a risk of? (2)
- Peri-partum disorder (3rd trimester) on eclampsia spectrum (usually increase BP and proteinuria)
- Labs: platelet count <100k, AST & ALT elevated more than 2x, bilirubin elevated, RBC fragments on peripheral blood smear, low serum haptoglobin <20, & LDH >600
- Risk of bleeding to mother, including hepatic hemorrhage
- Risk of placental abruption
What is the txt of HELP?
Treatment: Prompt delivery is main goal, IV magnesium sulfate to prevent seizures, anti-hypertensives, blood product transfusions
Fill in
What are the qualitative platelet disorders? (7)
- Von Williebrand’s Disease
- Drug induced
- Liver failure
- Renal failure (uremic platelet dysfunction)
- Cardiac bypass
- Inherited GpIb-IX or GpIIB-IIIa defects (ie Glanzmann Thromboasthenia or Bernard-Soulier Syndrome); very rare
- Inherited Platelet Storage Pool Disorder
What is the lab test for platelet function?
PFA-100®
VonWillibrands Disease:
* Deficiency or inhibition of what?
* What are the types?
* Usually _
* History of what?
* What form is rare? What is it associated with?
- Deficiency or inhibition of Von Williebrand Factor (vWF)-> platelet adhesion (platelet plug)
- Types 1(mc: mild)-4 ranging from mild to severe bleeding disorder
- Usually inherited
- Family history or personal history of excessive bleeding or platelet transfusions, especially mucocutaneous (mild bleeding)
- Acquired form is rare & associated with hypothyroidism, autoimmune diseases, & hematologic malignancies
VonWillibrands Disease
* how do you dx? (LABS)
- Diagnosed with ristocetin platelet test (plasma vWF activity)/ RIPA (tests platelet aggregation), quantitative vWF antigen, vWF multimer distribution, & factor VIII activity ELISA assay. PFA-100 abnormal, especially with types 2A, 2B, 2M, and 3.
- Other labs: Possible prolonged PTT (due to decrease in factor VIII activity) with normal PT & platelet count-> PT, INR normal so PFA
What is the txt of Vonwillibrands disease?
- Hemostatic medications (help you clot): DDAVP-desmopressin, aminocaproic acid, or tranexamic acid(ER)
- Replacement therapies: vWF concentrate and/or factor VIII concentrate (If you have major surgery)
Drugs that decrease platelet function
NSAIDs, aspirin, & clopidogrel (Plavix®)
- What does NSAIDs and aspirin inhibit?
- Aspirin & NSAIDs should be avoided when?
- NSAIDs and aspirin inhibit COX-1, which decreases production of thromboxane 2, so platelet aggregation is inhibited
- Aspirin & NSAIDs should be avoided in those with active bleeding, thrombocytopenia, or platelet dysfunction(VWD+Precedure)
- Also avoid in preoperative period (stop 7-30days) & if already on anticoagulants or SSRIs (GI bleeding)
Abnormal Coagulation Studies:
* PT prolonged, PTT normal:
* PT normal, PTT prolonged:
* Both PT & PTT prolonged:
- PT prolonged, PTT normal: Factor VII
- PT normal, PTT prolonged: Factors VIII, IX, XI, XII
- Both PT & PTT prolonged: Factors V, X
What are acquired coagulopathies? (4)
- DIC
- Liver Disease
- Vitamin K Deficiency
- Acquired inhibitors of coagulation
What are Inherited coagulopathies? (3)
- Hemophilia A
- Hemophilia B
- Von Williebrand’s Disease (factor VIII affected)
Hemophilias
* What type of disease?
* What is type A and B?
* What are the s/s
* What are the labs?
- X -linked recessive clotting factor deficiency
- Type A is factor 8 deficiency, type B is factor 9 deficiency (christmas)
- Signs/symptoms: severe bleeding, spontaneous hemarthroses, muscle hematomas, GI bleeding, bleeding with circumcision procedure(first clue)
- Labs: Prolonged PTT with normal PT; Factor 8 or 9 assay is diagnostic. Mixing study required to rule out clotting factor inhibitors.
What is the txt of hemophilias?
Treatment/Management: factor infusions, DDAVP, aminocaproic or tranexamic acid, avoid blood thinners (include OTC), avoid trauma/contact sports if severe
Vitamin K Deficiency
* Dietary vitamin K1/ phylloquinone found in what?
* Most often due to what?
* What are the sx?
- Dietary vitamin K1(greens), K2(GI flora)/ phylloquinone found in green vegetables like spinach
- Most often due to malnutrition, fat malabsorption (ie Celiac’s), or Warfarin
- Signs/symptoms: range from superficial bleeding (mild if early on) & easy bruisability to severe bleeds
Vitamin K Deficiency
* What are the labs and txt?
- Labs: PT prolonged to >4 times normal limit, PTT also prolonged if severe
- Treatment/Management: Treat underlying cause. Corrects with administration of supplemental Vitamin K (PO, IM, SubQ, IV). PO preferred if non-emergent bleeding
IV: risk with allergy
Liver Failure Associated Coagulopathy
* What is synthesized in the liver?
* What are the labs?
* Consider what?
- Fibrinogen, prothrombin, & most numbered factors are synthesized in the liver
- Labs: PT»PTT prolonged, INR>1.5, prolonged TT, possibly low platelet count
- Consider factor assays; factor V deficiency indicates liver failure over vitamin K deficiency
Decrease platelets dt liver making thrombintin and no coag factors
Liver Failure Associated Coagulopathy
* What is the txt?
Treatment: Administer fresh frozen plasma transfusion if bleeding
* has coag factors
Disseminated Intravascular Coagulopathy (DIC)
* What syndrome is this?
* What is overstimulated? What is that followed by?
* Results in what?
- Syndrome of widespread, acute, inappropriate triggering of 1° and 2 ° hemostasis
- Coagulation factors, fibrinogen & platelets overstimulated followed by rapid depletion
- Results in micro-occlusion of vessels resulting in organ failure & uncontrolled bleeding
- Medical emergency
Disseminated Intravascular Coagulopathy (DIC)
* What are the sxs?
Signs/symptoms: purpura, oozing from venipuncture sites, bleeding mucosal surfaces, gangrene, superficial thrombophlebitis, digital ischemia, severe hemorrhage of GI tract, respiratory distress, MI, CVA, seizures, hepatic failure, renal failure, shock
DIC:
* What are the labs?
* What is the txt?
- Labs: Prolonged PT and PTT, platelet count <100k (by the time of labs, in depletion phase), low fibrinogen (clotting factor), elevated D-dimer, elevated fibrin split products, peripheral blood smear with schistocytes
- Treatment/management: correct underlying cause, FFP or cryoprecipitate transfusion, platelet transfusion if bleeding predominates, tissue plasminogen activator (TPA) or low-dose heaprin if clots predominate
What are the causes of DIC?
Clotting Factor Inhibitors
* Auto-antibodies against what?
* Suspect when?
* High incidence?
* Also associated with?
- Auto-antibodies against a specific coagulation factor
- Suspect when clotting factor deficiency does not correct as expected
- High incidence with hemophilia
- Also associated with autoimmune disease (Autoantibodies), solid tumor cancers, and post-partum
SEREVE BLEEDING
What are the labs and txt of clotting factor inhibitor?
- Labs: Abnormal PT and/or PTT/INR
- 1:1 mixing study does not correct
- Most common is anti-factor VIII
- Treatment: Recombinant clotting factor when bleeding, steroids, cyclophosphamide, rituximab, emicizumab
Summary slide:
* Bleeding disorder occur as a result of what?
* Bleeding due to primary hemostasis/platelet disorder is usually more what?
* A platelet count <100k is clinically what?
* Thrombocytopenia most commonly occurs due to what?
* f platelet count and coagulation studies are normal in bleeding patient, need to rule out what?
* Coagulopathies include what?
What is the definition of anemia? How is it ID?
A reduction below normal in one or more of the following:
1. Hemoglobin (Hgb)
2. Hematocrit (Hct)-> 3 times hgb
3. RBC Count
Identified via complete blood count
What are the causes of por RBC production-> hypoproliferative?
- Iron deficiency
- Folic acid deficiency
- Vitamin B12 deficiency
- Anemia of chronic disease
- Hypothyroidism/-gonadism
- Bone marrow suppression or failure (malignancy, medications, aplastic anemia)
CHI AF
What are the causes of poor RBC production-> ineffective or unstable erythropiesis?
- Sickle cell anemia
- Thalassemias
- Sideroblastic
- Methoglobinemia
What are the causes of rbc destruction anemia?
Hemolysis
-Autoimmune -G6PD deficiency
-PNH
-TTP/HUS
-Infections
-Thalassemias and sickle cell
-Hypersplenism
What are the casues of loss of RBC anemia?
What are microcytic, macrocytic and normocytic anemias?
What the microcytic anemias?
What are the macrocytic anemias?
What are macrocytic (nonmegaloblastic) anemias?
What are the normocytic anemias?
- What is MCV? (micro vs macro)
- What is MCHC? (what are hypo and hyper)
- What is MCH?
- What RDW?
What is the variation in size and shape called?
Abnormal RBCs on Peripheral Blood Smear
- Target cells-
- Burr cell-
- Tear drop cell-
- Schistocytes-
- Target cells- thalassemia, liver disease, hemoglobin C
- Burr cell- liver disease, renal disease
- Tear drop cell- myelofibrosis
- Schistocytes- microangiopathic hemolytic anemia
Abnormal RBCs on Peripheral Blood Smear
- Howell jolly bodies-
- Basophilic stippling-
- Acanthocytes-
- Elliptocytes-
- Howell jolly bodies- splenectomy
- Basophilic stippling- lead poisoning
- Acanthocytes- liver disease
- Elliptocytes- iron deficiency, thalassemia
Abnormal RBCs on Peripheral Blood Smear
- Stomacytes-
- Sickle cells-
- Rouleaux formation-
- Sideroblasts-
- Stomacytes- alcoholic liver disease
- Sickle cells- sickle cell disease
- Rouleaux formation- multiple myeloma
- Sideroblasts- myelodysplastic syndrome
What are two important questions do you need to know when approaching an anemic patient?
Low yield
What are others questions do you need to know about anemic patients?
Systemic Effects of Anemia
* What are consitutional?
* What are cardio?
* What is respiratory?
* What is integumentary?
- Constitutional: fatigue (likely if Hgb <10), dizziness, general weakness, reduced exercise capacity
- Cardiovascular: tachycardia, palpitations, systolic murmur, hypotension if due to acute bleeding, angina if severe
- Respiratory: dyspnea, tachypnea
- Integumentary: reduced perfusion- delayed capillary refill, pallor of skin, oral mucosa, & conjunctiva, cold & brittle nails
Systemic Effects of Anemia
* Renal?
* GI?
* Neurological?
* GU?
- Renal: reduced perfusion, proteinuria, fluid retention
- Gastrointestinal: indigestion
- Neurological: cognitive function, mood, vertigo
- GU: menstrual disturbances, loss of libido, impotence
Vitamin/mineral deficiency is the result of one of five processes:
Iron (Fe) Deficiency Anemia
* Due to what?
* Food rich in FE include what?
* Most often due to what ⭐️ When should you suspect it?
* Second most common what?
- Due to negative iron balance (not enough)
- Foods rich in Fe include meat, fish, eggs, leafy greens, & beans (animal and plants)
- Most often due to bleeding! Suspect it’s a secondary disorder in young children, adult men, and post-menopausal women
- Second most common underlying disease is a malabsorption disorder
Iron (Fe) Deficiency Anemia
* What are the sxs?
Signs/symptoms: pica (ie ice), koilonychia “spoon nails”, cheilosis, dysphasia (Plummer Vinson Syndrome), or CNS symptoms if severe
Iron Deficiency Anemia
* What are the labs?
* What are the txt?
What does this show?
Decrease iron-> hypochronic
Megaloblastic Anemias-
Vitamin B12 (cobalamin) deficiency
* Vitamin B12 is normally does what?
* Essential for what?
* Found in what?
* Deficiency most often due to what?
What are the sxs of Vitamin B12 deficiency?
Signs/symptoms: glossitis-smooth, beefy red tongue, paresthesias, peripheral neuropathy, impaired proprioception and/or vibratory sense, balance difficulty, psychosis or dementia possible, anorexia, weight loss, diarrhea
What are the labs and txt of vitamin B12 deficiency?
Pernicious Anemia
* What is it?
* Occurs in who?
* What is the median age?
* What may be found in serum?
* DX how?
Megaloblastic Anemias- Folic Acid Deficiency
* Folic acid is normally is what?
* Found in what?
* Patients at risk?
- Folic acid is normally ingested, absorbed in jejunum, circulates unbound as 5-methyl-THF, & requires B12 to enter the cells
- Found in green leafy vegetables, liver, fruits, & nuts
- Patients at risk: malnutrition (alcoholics, elderly), dietary deficiency, tropical sprue, medication effect (ie Bactrim, phenytoin, methotrexate), pregnancy (increase demand so prenatal vit needed), loss due to hemodialysis
Megaloblastic Anemias- Folic Acid Deficiency
* What are the labs?
* What are the txt?
- Labs: Macrocytic & normochromic anemia, high RDW, & low serum & RBC folate levels
- Treatment: Oral Folic acid 1-5, but up to 15mg daily for 2-4 months
Sideroblastic Anemias
* Disorders of what?
* What are examples?
* What are the labs?
- Disorders of ineffective erythropoiesis; iron not correctly incorporated into RBC
- Examples: myelodysplastic syndrome, lead poisoning, Vit B6 deficiency, Cu deficiency, alcoholism, drugs (ie isoniazid), hereditary
- Labs: may be microcytic (ie hereditary) or macrocytic (ie alcoholism & MDS)
Sideroblastic Anemias
* What is the dx?
* What may it lead to?
* What is the txt?
- Diagnostics: ringed sideroblasts on bone marrow biopsy
- May lead to hemochromatosis
- Treatment: treat underlying cause (ie pyridoxine)
Anemia of Chronic Kidney Disease
* Due to what?
* What are the labs?
* What is the txt?
Anemia of Chronic Disease/Inflammation
* Caused by what?
* What is it associated it what?
- Caused by increase in proinflammatory cytokines which decrease erythropoiesis
- Associated with chronic infection (TB, chronic UTI), autoimmune diseases (ie SLE, RA), malignancies, liver disease, alcoholism*, hypo- or hyperthyroidism
*Usually macrocytic
Anemia of Chronic Disease/Inflammation
* What are the labs?
* What are the txt?
- Labs: Normocytic or microcytic, normochromic anemia. Ferritin level elevated in response to inflammation. (look at iron levels, then ferritin level)
- Treatment: Address the underlying cause. May support with RBC transfusions and exogenous EPO. (IL-1 can lower EPO)
Aplastic Anemia
* Bone marrow failure resulting from what?
* Presents as what?
* Diagnosed via what?
* What are causes?
- Bone marrow failure resulting from damage to hematopoietic stem cells
- Presents as profound anemia plus leukopenia plus thrombocytopenia (low of all counts)
- Diagnosed via bone marrow biopsy
- 65% of cases are idiopathic
- Other cases due to SLE, chemotherapy, toxins (benzene), drugs (ie phenytoin, NSAIDs), viruses (EBV), radiation poisoning, Fanconi anemia
What is the txt of Aplastic Anemia?
Treatments: transfusions, anti-thymocyte globulin, cyclosporine, cyclophosphamide, allogeneic bone marrow transplant
hemolytic anemias
* Due to what?
* results in what?
What becomes enlarged in hemolytic anemias?
Hemolysis Lab Findings
* What is high?
* What is low?
* What is on blood smear?
* What is UA?
* What test?
High:
* Elevated reticulocyte count and/or reticulocyte production index
* Elevated unconjugated/indirect bilirubin level
* Elevated lactate dehydrogenase (LDH)
Low
* Low hemoglobin with high MCV and high RDW -> macrocytic anemia
* Low haptoglobin level
peripheral blood smear
* RBC fragments, ie schistocytes
Urinalysis with hemoglobinuria
Direct Coombs/Antiglobulin Test
What is the Direct Coombs/Antiglobulin Test
is postive and negative with hemolysis anemia?
- If positive, autoimmune, drug related, transfusion, infection, or cancer.
- If negative, G6PD deficiency, PNH, TTP/HUS, or DIC.
Reticulocytes
* What are they?
* What is there size?
* Reported as what?
* When is it elevated?
Classification of Hemolytic Anemias-> Intrinsic/Intravascular
* What are causes?
- Membrane defects: PNH, hereditary spherocytosis, hereditary
- elliptocytosis
- Glycolytic defects: pyruvate kinase deficiency
- Oxidation vulnerability: G6PD deficiency
- Hemoglobinopathies: sickle cell
- Vigorous exercise
Classification of Hemolytic Anemias->Extrinsic/Extravascular
Autoimmune Hemolytic Anemia
* Caused by what?
* What are casues?
* 10% have concomitant ITP?
* What are the labs?
* What are the txt?
G6PD (glucose6-phosphate dehydrogenase) Deficiency
* What type of disease?
* What is the mc population?
* Decreased ability of RBCs to deal with what?
* What are the labs?
* What is the txt?
What are the oxidative drugs?
Paroxysmal Nocturnal Hemoglobinuria (PNH)
* What type?
* Abnormal sensitivity of what?
* Results from what?
* What are the sxs?
- Inherited & rare
- Abnormal sensitivity of RBCs to lysis by complement, especially at night
- Results from somatic mutation in the PIG-A gene
- Signs/symptoms: Episodic hemoglobinuria (reddish brown) in a child, most often with first micturition in the morning
Paroxysmal Nocturnal Hemoglobinuria (PNH)
* What are the labs?
* What is the txt?
Post-Hemorrhagic Anemia
* What are the two types?
* What are the labs?
* What is the txt?
- What is the txt of GI bleed?
- How can you see a bleed?
What does this show?
Hemoglobinopathies
- Disorders of what?
- Most are what?
- What screening is what common?
- what are the types?
- Disorders of globin synthesis or stability; lead to anemia
- Most are inherited
- Peri-partum screening is common
- Types: Thalessemias, Sickle Cell Disorder, & others
What is the normal adult hemoglobin?
- Hemoglobin= heme + 4 globin units (2 alpha chain genes and 2 beta)
- Heme= iron + 4 protoporphyrins
Hemoglobin Electrophoresis
* What are the different types?
Thalassemias
* Inherited disorderes with what?
* Results in what?
* What are the labs?
* What is on the peripheral smear?
Thalassemias
* Severity varies widely ?
from asymptomatic carrier status to severe anemia with extramedullary hematopoiesis, skeletal changes, hepatosplenomegaly, & hemochromatosis
What is this?
Beta Thalassemias
* Trad in what?
* What is major?
* Intermedia?
* Minor/carrier/trait?
Alpha Thalassemias
* Traditionally in what?
* What is major?
* What is intermedia?
* What is minor/a1 trait?
* What is minima/carrier/a2 trait?
What is this?
Sickle Cell Anemia
* caused by what?
* Hgb reversibly does what?
* Results in what?
* How long can pain last?
* What indicated poor prognosis?
* What is most prevalent pop?
* What is sickle cell trait?
Why is sickle cell painful?
End Organ Damage due to Sickle Cell Crises
* What is an important what?
* What is acute chest syndrome due to what?
* Cognitive and behavioral abnormalities possible due to what?
Diagnosis & Treatment of Sickle Cell?
Methemoglobinemia “Blue Man Syndrome”
* What type of disease?
* Methemoglobin is generated by what?
* What is it caused by?
* What does it result in?
* Often identified via what?
* What is txt?
Summary page:
* Anemia is a common finding on what?
* Anemias are due to what?
* Once anemia is identified by what ?
* Microcytic, hypochromic anemias include what?
* Macrocytic anemias include what?
* Hemoglobinopathies such as what?
