Hematology and Fetal Surgery Notes

Platelet Counts and Function

• Platelet counts of 75-80 can still indicate impaired function if uremia is present due to significantly high BUN.
• Uremia can lead to spontaneous bleeding even with a fairly normal platelet count.
• High platelet count is thrombocythemia or thrombocytosis.
  • This can be caused by a disease or condition.
  • Often seen with inflammation.
• Reduction of all cell lines is pancytopenia.

Iron Overload

• Iron overload occurs when there is too much iron absorbed or absorption issues.
• Commonly seen in patients receiving multiple red cell transfusions.
  • Concerns arise due to the high iron load.
• Can also result from excessive intake of iron-containing products (e.g., vitamins).
• Chronic hepatitis can lead to inflammation and increased ferritin levels, contributing to iron overload.

Hemochromatosis

• A genetically linked condition causing inappropriate regulation of iron absorption, transport, and storage.
• Leads to iron accumulation in organs such as the liver, thyroid, pancreas, heart, gonads, skin, and pituitary glands.
• Iron deposition can cause tissue damage, inflammation, and fibrosis/destruction of organs.

Types of Hereditary Hemochromatosis

• Type 1:
  • Onset typically in men aged 40-60, and in women after menopause.
  • Most common type.
• Type 2:
  • Onset usually in childhood.
• Type 3:
  • Onset ranges between childhood and 40-60 years.
• Type 4:
  • Onset generally in men around age 40-60.

Anemias

• Signs are directly linked to the need for red blood cells for oxygen carrying capacity. Without appropriate red cells to be able to carry oxygen to target tissues, we see cellular and tissue hypoxia.
• Cellular and tissue hypoxia leads to weakness, fatigue, pallor, syncope, dyspnea, and tachycardia.
• The body's ability to compensate for anemia depends on the quickness of onset.
  • With slower, more progressive destruction or poor replacement of red cells, signs and symptoms aren't significant or sudden.

Etiology of Anemias

• Acute or chronic blood loss (e.g., chronic GI bleeds).
• Decreased erythrocyte production (e.g., renal failure due to inadequate erythropoietin production).
• Increased erythrocyte destruction (e.g., sickle cell anemia, ABO incompatibility, spherocytosis).
  • Can be due to immune antibody attack causing earlier destruction or abnormal red blood cell shapes (sickle or sphere).
• Combinations of the above.

Diagnosing Anemia

• Diagnose with MCV (mean corpuscular volume).
  • Low MCV (microcytic/small red blood cell):
    • Iron deficiency: Insufficient iron for proper red blood cell size.
    • Thalassemia.
    • Lead poisoning.
  • Normal MCV:
    • Acute bleeding
    • Anaplastic anemia.
    • Hemolytic anemia: Normal-sized cells being produced but not in sufficient quantity.
  • High MCV (macrocytic/large red blood cell):
    • Pernicious anemia.
    • Low folate.

Iron Deficiency Anemia

• Most common form, especially in genetic females, children, and the elderly.
  • Related to not enough dietary intake.
• Manifestations:
  • Cyanotic sclera, brittle nails, decreased appetite, irritability, stomatitis, pica, delayed healing.
• Long-term, uncorrected iron deficiency can lead to neurocognitive impairment.
• Causes:
  • Lack of dietary intake.
  • Decreased ability to absorb iron.
  • Losses due to GI bleeding, GI cancer, menstruation.
• Red blood cells are microcytic (smaller) and hypochromic (pale).

CBC Findings

• Low hemoglobin and hematocrit.
• Low MCV.
• Low serum ferritin and serum iron.
• Transferrin saturation is usually high.
• TIBC (total iron binding capacity) is high.

Further Tests

• Fecal occult blood test (to check for GI losses).
• Colonoscopy and endoscopy (to look for bleeding ulcers or other lesions).

Treatment and Management

• Iron supplementation.
• Evaluation of diet and possible intestinal absorption issues (e.g., celiac disease).

Aplastic Anemia

• Enough iron in the diet, but bone marrow depression occurs.
• Causes:
  • Idiopathic, autoimmune, treatments, viral, or genetic.
• Development can be insidious or sudden.
• Manifestations:
  • Pancytopenia, leading to bleeding (thrombocytopenia), fevers/infections (neutropenia), and fatigue (anemia).
  • Prolonged bleeding after venipuncture or at insertion sites.

Diagnosis

• CBC for initial screening.
• Bone marrow biopsy to show depression of cell lines.

Treatment and Management

• Identify and address the cause.
• Medication review (med rec important).
• Oxygen supplementation.
• Manage signs associated with pancytopenia (transfusions for bleeding, treat infections).
• Vaccinations and precautions to prevent infection.
• Bone marrow transplant (curative).
• Immunotherapy (especially if autoimmune).

Hemolytic Anemia

• Normal red blood cell size, but excessive destruction (hemolysis) occurs.
• Causes:
  • Idiopathic, autoimmune, genetic links, infections, blood transfusion reactions, blood incompatibility (ABO or Rh incompatibility between pregnant individual and fetus).
• Sickle cell anemia is an example.
  • Hemoglobin S causes erythrocytes to carry less oxygen and have an abnormal shape.
  • Abnormal shape causes vessel clogging, leading to hypoxia and ischemia downstream.
  • Sickled cells are also destroyed.
• Manifestations: usually demonstrate around 4 months of age, during the transition from fetal to adult hemoglobin.

Signs

• Sickle crisis (triggered by dehydration, stress, altitude, fever).
• Pain (lower back, chest, abdomen, long bones) - acute and chronic (neuropathic).
• Hyperalgesia and opioid sensitization.

Diagnosis

• Hemoglobin electrophoresis.
• CBC.
• Bilirubin (to assess lysis).

Management

• Improve life expectancy.
• Genetic modifications with CRISPR (potentially standard of care):
  • Bone marrow makes fetal hemoglobin (which does not sickle) instead of hemoglobin S.
  • Shorter lifespan (30 days) compared to adult hemoglobin (120 days).
  • Monitor for chronic anemia and ensure adequate iron and B12.

Diseases of Leukocytes

• Includes leukemias, lymphomas, and myelomas.

Leukemia

• Blood cell origin: Hematopoietic.
• Diagnostics:
  • Bone marrow.
  • CBC (with blast cells).
• Abnormal white cells take over the bone marrow space, leading to:
  • Anemia.
  • Thrombocytopenia.
  • Infections and bleeding.

Lymphoma

• Blood cell origin: Hematopoietic.
• Diagnostics:
  • Bone marrow.
  • CBC
  • Reed-Sternberg cells.
• Risk for infections.

Myeloma

• Blood cell origin: Plasma.
• Diagnostics:
  • Bone marrow.
  • Myeloma protein.
  • Monoclonal protein or paraproteins.
• Compression fractures are a sign.

Leukemia Details

• Cancer involving leukocytes.
• Abnormal leukocytes travel through the circulatory system, impacting different organs (bone marrow).
• Abnormal production, proliferation, and differentiation of leukocytes.
• Abnormal leukocytes might not die when they're supposed to, leading to crowding of normal cells. Which leads to potential for strokes and ischemia.
• Grouped based on cell lines (myeloid or lymphoid) and acuity (acute or chronic).
• Risk factors: Mutagens, chemo, other diseases, genetic links.
• Acute leukemias: Rapid onset and progression.
• Chronic leukemias: Insidious, less aggressive.

Signs and Symptoms

• Pallor, fatigue, weakness, dyspnea, dizziness (due to crowding out red cells).
• Bleeding (crowding out platelets).
• Lymphadenopathy.
• Splenomegaly or hepatomegaly.
• Night sweats, unexplained weight loss, fever, abdominal pain, and fullness.
• Fever (due to poor white blood cell function).

Genetic Links in Chronic Leukemias

• Translocations, e.g., Abelson proto-oncogene on chromosome 9 to 22 (Philadelphia chromosome).
• Translocations in adults: chromosomes 4 and 11 or nine and twenty-two.

Lymphomas

• Hematopoietic, look for Reed-Sternberg cells.
• Hodgkin's lymphoma vs. non-Hodgkin's lymphoma.
• Viral links with both, including HIV and Epstein-Barr.
• Difference between subtypes depends on cell appearance under microscope.

Multiple Myelomas

• Cancers arising from B cells, plasma cells.
• Associated with chromosomal abnormalities (translocations).
• Genetic abnormality in B cells during development in the bone marrow.
• Abnormal plasma cells go into the bone marrow in huge numbers, causing bone destruction and impacting hematopoiesis.
• Can lead to:
• Fractures and hypercalcemia (due to bone destruction).
• Pancytopenia (reduction of all cell lines).

Diseases of Coagulation

*Clotting factors are inactive until activated. Cascade dependent on calcium and vitamin K.

Intrinsic Pathway

• Initiated by activation of the Hageman factor.
• Activated factors are enzymes.

Extrinsic Pathway

• Activated by exposure of tissue factor (tissue damage/injury).
• Tissue factor complexes with factor VII, activating it and forming further complexes.

Application

Platelet count. Not only have enough platelets, but they have to be able to function appropriately. Uremia can cause poor platelet function.

• Bleeding time (2-9 minutes):
  • Assesses platelet function.
  • Delayed with von Willebrand deficiency, NSAIDs, aspirin, valproic acid.
• Prothrombin time (PT):
  • Represents function of factors II, V, VII, and X (made by the liver, require vitamin K).
  • An elevated PT indicates vitamin K deficiency.
• INR: Estimates percent of functional clotting factors.
• PTT: Measures efficacy of von Willebrand factor and other factors.

Hemostasis

• Balance between clotting and bleeding.
• Requires prostacyclin, antithrombin III, and nitric oxide (in endothelial cells).

Primary Process

• Injury to blood vessel -> vasoconstriction (local) to decrease blood loss.
• Platelets can't attach due to nitric oxide and prostacyclin.
• Injury/trauma decreases nitric oxide and prostacyclin, allowing platelet adhesion to cell membrane edge -> platelet plug.
• Endothelial lining secretes von Willebrand factor, which binds to basement membrane and platelets will also bind to it. Platelets then release substances, changing shapes to help this become stronger.

Secondary Process

• Platelets release fibrinogen and calcium.
• Release of thromboxane A2 further vasoconstricts and opposes prostacyclin, promoting platelet aggregation.
• Enzyme thrombin activates fibrinogen to become fibrin.
• Fibrin attaches to platelets, solidifying in the area to making it a platelet plug.

Von Willebrand's Disease

• Most common inherited bleeding disorder (four types).
• Doesn't usually cause spontaneous bleeding.
• Caused by genetic deficiency of von Willebrand factor, leading to issues in platelet aggregation and it's ability to adhere to damaged blood vessel wall.

Manifestations

• Lengthened bleeding time.
• Treat with cryo or desmopressin (DDAVP).
• Cryo has von Willebrand factor.

Hemophilia

• X-linked recessive bleeding disorder.
• Classified by spontaneous bleeding vs. bleeding after trauma/surgery.
• Two kinds:
  • Hemophilia A (classic hemophilia): Factor VIII deficiency.
  • Hemophilia B (Christmas disease): Factor IX deficiency.
• Diagnosis usually made by one month.
  • Spontaneous bleeding or bleeding with circumcision or venipuncture.

Signs

• Persistent bleeding from minor wounds, bruising/swelling of joints from hemarthrosis.
• Prolonged PTT, normal PT.
• Check factor VIII for hemophilia A and factor IX for hemophilia B.
• Treat with replacing the particular factor (VIII or IX).

DIC (Disseminated Intravascular Coagulation)

• Treat the underlying problem.
• Tissue damage or endothelial damage/intrinsic pathway impact.
• Want to consider administering cryo, FFP, platelets when administering transfusions.
• Extrinsic: Heparin to prevent micro-clotting.
• Production of thrombi and activation of fibrinolytic system (breaks down clots).

Manifestations

• Significant bleeding.
• Micro and macro clotting.
• Altered mental status, seizures, angina, tachycardia, hypotension, oliguria.
• Symmetric cyanosis due to microthrombi.
• Organ damage (elevated liver enzymes).

Causes

• Sepsis, tissue factor particles, burns, head injury, release of procoagulants from injuries, transfusion reactions, cancer, pregnancy complications, recent surgery/anesthesia, severe liver disease, cardiac arrest, poisonous snake bites.

Diagnostics

• Low platelet count, prolonged clotting studies, high D-dimer, low fibrinogen function, low ATIII, protein C and protein S.

Treatment and Management

• Prevent clotting and bleeding (support and treat the underlying etiology).

Platelet Dysfunction

• ITP (immune thrombocytopenic purpura) is a good example.
• Hypercoagulability due to autoimmune destruction of platelets.

Pathophysiology:

• Acute ITP generally is self limiting, and is common in kids with sudden onset.
• Chronic is more common in women between the ages 20 to 50
• acute ITP is more common than chronic in children
• Also Uremia patient with tongue tie, there might need to be a phrenulectomy.

Manifestations

• Usually bleeding and clotting.

Etiology

• Viral, autoimmune, live vaccine immunization.

Diagnostics

• Platelet count, bleeding studies, clotting cascade, CBC.
• A med rec is very important, and consider proximity to vaccination.

Management

• Steroids (decrease immune response).
• Immunoglobulins (augment immune system}.
• Plasmapheresis (remove autoimmune components or viral infection).
• Splenectomy (only if being the cause, or the source for the sequesters of platlets).
• Blood transfusions (ensure enough blood volumes and the components).
• immunosuppression treatment; and platlet phoresis

Fetal Surgery

*Fetal surgery is not on the exam

• Maternal-fetal care centers can provide team for fetal surgery.
• CRNA's may be in cases that involve fetal surgery

Pregnancy-Associated Cardiovascular Changes

• Cardiac output increases 40% to provide enough O2 to uterus and fetus.
• Drop in blood pressure (progesterone-mediated decrease in systemic vascular resistance).
• Plasma volume, resting heart rate, stroke volume increase; autonomic nervous system tone increases.

Structural Changes

• Remodeling of myocytes, increase in LV and RV wall mass and thickness.
• Dilation of all heart chambers.

Implications for Anesthesia

• Maternal blood pressure remains normal to maintain uterine blood flow.
• Manage maternal pain and anxiety without causing over/under sedation or analgesia.
• Manage maternal hypotension without influencing the fetus
• Sympathetic tone, neuraxial vasodilating drugs or even IHAs, can cause hypotension

Respiratory Changes

• Increased metabolic demand.
  • 60% increase in CO2 consumption and production.
• Diaphragm displaced upward (gravid uterus), causing barrel shape, and decreases functional residual capacity.
• Rapid O2 desaturation during apnea related to induction.
• Upper airway edema and tissue friability.
• In pregnancy, their is increaseed sympathtetic tone in pregnancy
  Compensatory mechanisms exist in a fetus they are fussy little nuggets, so there for they are very dependent..

Implication for Anesthesia

• Pre-induction pre-oxygenation is generally required, and very important, especially in the setting of edema.
• Airway assessment is important, and consider being ready with many types of intubation available

Blood Flow

• Maintain cardiac output, and stroke volume (uterine contractions decrease uterine blood flow).
• Treat contractions with smooth muscle relaxants/tocolytics (high-dose inhaled volatile agents, Mag, nitroglycerin, indomethacin, terbutaline).
• Monitor blood pressure (smooth muscle relaxants can cause maternal hypotension).
  Maintain blood flow
• Have adequate O2 support for the mother
  *Fetal Concerns
  ** mitigate the fetal response to noxious stim
  ** Immobilize that the fetus, with fentanyl, but fentanyl can cause low HR which is why morphine is preferre, and atropine, and bec are given to fetus

Anesthetic Goals Based on Type of Fetal Surgery

• Open fetal surgery.
• Fetoscopic.
• EXIT procedure (for big airway masses).
• C-section. Anesthesia of choice is regional, could be general or regional.

Decisions Regarding Neuraxial vs. General

• Maternal refusal of neuraxial.
• Favoring neuraxial: aspiration risk, difficult airway, if patient wants to witness the birth.
• Fetal conditions, anesthesia concerns, and surgical concerns will also come into play.

Conclusion

• Keeping with blood flow: Maintaining cardiac output and stroke volume and a certain amount of blood volume is critical.