Diseases of RBC & Bleeding Disorders I PDF

PATHOLOGY | TRANS #5A LE Diseases of RBC & Bleeding Disorders I DR. ARACELI P. JACOBA, MD FPSP | 10/03/2024 | Version...

PATHOLOGY | TRANS #5A LE Diseases of RBC & Bleeding Disorders I DR. ARACELI P. JACOBA, MD FPSP | 10/03/2024 | Version #1 02 OUTLINE Liver I. Introduction to IV. Hemolytic Disorders → Main hematopoietic organ in the fetus from 4 weeks Hematopoiesis A. Hereditary until the child is born producing majority of the blood A. Site of Hematopoiesis Spherocytosis requirements of the fetus B. Hemoglobin Structure B. Glucose-6-Phosphate Bone marrow C. Normal Hematopoiesis Dehydrogenase → At birth, bone marrow takes over the liver as the main D. Red Cell Maturation Deficiency hematopoietic organ II. Anemia C. Sickle Cell Anemia A. Signs and Symptoms D. Thalassemia → Liver is no longer active unless there is anemia in the B. Physical Examination E. Paroxysmal developing fetus like in hydrops fetalis causing C. Laboratory Diagnosis Nocturnal extramedullary hematopoiesis D. Red Blood Cell Indices Hemoglobinuria → When a child is born, all the bones are active, but as E. Peripheral Blood Smears F. Autoimmune one grows older, the long bones contribute lesser and F. Classification According to Hemolytic Anemia lesser to hematopoiesis Morphology G. Microangiopathic → At 18 years old, only the central bones (vertebrae, G.Causes of Anemia Hemolytic Anemia pelvis, sternum, and ribs) are hematologically active III. Hemolytic Anemia V. Summary A. General VI. Review Questions → At about 40 to 50 years old, there is minimal or no Characteristics VII. References contribution from femur or long bones in the B. Intravascular hematopoietic activity (50% of the marrow remains Hemolysis active in the adults) C. Extravascular → Samples for bone marrow aspirates are obtained from Hemolysis the pelvic bones as it is the bone that has the most D. Histology hematopoietic activity throughout a patient’s lifetime Must Lecturer Book Previous Youtube → Pathologic conditions: ❗️ Know 💬 📖 📋 Trans 🔺 Video ▪ Long bones and skull can develop hematopoietic activity in anemia SUMMARY OF ABBREVIATIONS ▪ More bones are recruited for hematopoiesis, the more severe the anemia is HbF Hemoglobin F HSC Hematopoietic Stem Cells Hb Hemoglobin Hct Hematocrit PBS Peripheral Blood Smear MCV Mean Corpuscular Volume MCHC Mean Corpuscular Hemoglobin Concentration MCH Mean Corpuscular Hemoglobin RBC Red Blood Cell PNH Paroxysmal Nocturnal Hemoglobinuria IHA Immunohemolytic Anemia AHA Autoimmune Hemolytic Anemia SLC Systemic Lupus Erythematosus DIC Disseminated Intravascular Coagulopathy Figure 1. Organs involved in hematopoiesis[Lecture PPT] TTP Thrombotic Thrombocytopenic Purpura RES Reticuloendothelial System HEMOGLOBIN STRUCTURE Hemoglobin structure varies during development LEARNING OBJECTIVES In the fetus, the red cell contain HbF ✔ To understand the different types of anemia, its causes, → Consist of alpha-2, gamma-2 globin chain symptomatology, laboratory diagnosis based on RBC → Allows easier release of O2 in tissues despite the alterations and prognosis relative hypoxia in developing fetus ✔ To understand hemolysis → Main hemoglobin at birth and decreases until about 6 ✔ To understand bleeding disorders months of age I. INTRODUCTION TO HEMATOPOIESIS → Some hematologic diseases start to manifest symptoms SITE OF HEMATOPOIESIS only at 6 months when HbF is no longer present in the Yolk sac blood → First organ responsible for the production of blood in the Adult hemoglobin fetus → 95% HbA (α2β2) → Starts as early as 4 weeks or 1st month of → 3-5% HbA2 (α2δ2) embryogenesis until the 3rd month HbA1C is a subtype of HbA increased in diabetic patients Spleen → Used in monitoring sugar levels → Takes over the yolk sac at 3rd month → It is not involved in hematologic disorders → Minimal contribution since majority of hematopoiesis Hemoglobin containing Epsilon and Zeta are very occurs in the liver immature forms produced in the yolk sac LE 2 TG 4 | Aquino K., Aquino R., Aranda, Arceo TE | Antonio AVPAA | Boque PAGE 1 of 14 TRANS 5A VPAA | Cambas PATHOLOGY | LE 2 Diseases of RBC & Bleeding Disorders I | Araceli P. Jacoba → Once the liver takes over hematopoiesis, these are lost Intravascular space (below horizontal orange line in Figure in the system 3) → Cells beyond blood vessels ▪ Monocytes → macrophages ▪ Basophil → mast cells ▪ B-lymphocytes → plasma cells Table 1. Stimulatory controls to hematopoiesis Cells Stimulatory Control Pluripotent stem cells in Stem Cell Factor (SCF) production of more and cytokine IL-6 myelocytes Myeloid stem cells Stem Cell Factor (SCF), cytokine IL-3 and IL-6 Erythrocyte production Erythropoietin (EPO) Figure 2. Hemoglobin Structure[Lecture PPT] Platelet production Thrombopoietin (TPO) NORMAL HEMATOPOIESIS RED CELL MATURATION Pluripotent stem cells → Most immature stem cells that can differentiate to blood or mesenchyme of any organ Hematopoietic Stem Cells (HSC) → A pluripotent/multipotent cell capable of self renewal → It is specific for hematopoietic cells and the start of hematopoiesis → Two important characteristics: ▪ Pluripotency: ability of a single HSC to generate all mature blood elements ▪ Self-renewal: provides on daughter cell that is renewed as HSC to prevent depletion, this cell is collected for bone marrow transplant ❗️ HSC into to separate stem cells or progenitor cells → Myeloid stem cells ▪ Produce red blood cells, platelets, neutrophils, ❗️ monocytes, eosinophils, basophils ▪ Red blood cells and platelets originate from the same stem cells that produce granulocytes and Figure 4. Erythropoiesis[Lecture PPT] monocytes Maturity involves the following characteristics: − Some diseases of RBCs will have problems with → Decrease in cell size platelets and granulocytic WBC when myeloid → Condensation of the chromatin (pyknotic) and loss of stem cell is involved in disease nucleus → Lymphoid stem cells → Change in the color of cytoplasm from blue to red as it ▪ Produce B and T lymphocytes takes more hemoglobin Erythropoietin → Stimulates BFU-E/proerythroblasts (cell before pronormoblast, after myeloid cells) to develop red blood cells → Entire erythropoietic development takes 3 to 5 days CELLS IN RBC DEVELOPMENT Pronormoblast → Largest and most immature cell: large nucleus, present nucleoli, and blue cytoplasm → Followed by 3 normoblasts Basophilic Normoblast → Dark blue cytoplasm, denser chromatin, and with nucleoli present Polychromatic Normoblast → Cytoplasm is polychromatophilic (ie. mixture of red and blue), has a smaller nucleus without a nucleoli Orthochromatic Normoblast → Cytoplasm is orange/reddish with very dense ink blot nuclei Figure 3. Cells involved in hematopoiesis[Lecture PPT] Polychromatophilic Erythrocyte/Reticulocyte Red arrows pertain to stimulatory controls to → No nucleus hematopoiesis → First cell present in the peripheral blood PATHOLOGY Diseases of RBC & Bleeding Disorders PAGE 2 of 14 PATHOLOGY | LE 2 Diseases of RBC & Bleeding Disorders I | Araceli P. Jacoba Mature red cell/Erythrocyte ANEMIA Reduction of the total circulating red cell mass to below normal limits resulting in decreased oxygen transport → Not concerned with any other content of blood, only concerned with the number and volume of red blood cells and its hemoglobin content SIGNS AND SYMPTOMS Nonspecific; attributed to the decrease in O2 supply → Weakness, malaise, easy fatigability, dyspnea on mild exertion, headache, dizziness Figure 6. Pallor in the palm of hands (left)[Lecture PPT] Same manifestations can be seen in diseases of the heart, lungs, patients with malignancies, or even prodrome of and infection PHYSICAL EXAMINATION Pallor → Most consistent finding of anemia ▪ Best seen on conjunctiva, floor of the mouth and palms of the hands → Examining skin is subjective; NOT a good method to evaluate pallor since skin tone varies according to race Figure 7. Koilonychia[Lecture PPT] and may obscure the presence or absence of anemia Murmurs LABORATORY DIAGNOSIS → Called “hemic murmur” Since symptoms of anemia are nonspecific and physical → Characterized by being low grade (1 or 2 over 5) and exam can be subjective, a diagnosis of anemia needs a systolic, otherwise it might be a pathologic cardiac laboratory confirmation murmur Hemoglobin (Hb) and Hematocrit (Hct) → Due to the decreasing viscosity of the blood, creating → Determines the level of anemia turbulence in the cardiac chambers during systole → Values below normal indicates anemia Angina → Normal values vary depending on age, sex, race and → May be present when there is compromised location oxygenation in the heart with an occluded coronary ▪ Males > Females vessel − Higher normal value in males due to monthly Oliguria (decreased urine volume) & anuria (no urine) losses during menstruation in females → Present only if blood loss is the cause of anemia ▪ Living in highlands > lowlands → If the cause of anemia is hemoglobinopathy or ▪ Caucasians > Asians nutritional anemia, it will not cause oliguria ▪ Slightly decreases in the elderly Brittle nails or koilonychia (spooning of the nails) ▪ High levels seen in the newborn → In chronic and persistent decreased O2 supply to nail Reticulocyte count: 0.5-1.5% beds (prolonged oxygen deprivation in the nail beds) → Determines bone marrow response to anemia → Not specific for anemia and may also be seen in chronic ▪ Functioning bone marrow: reticulocytes are lung disease elevated in the presence of anemia as a response to ❗️ RBC loss ▪ Non-functioning marrow: reticulocyte count is NOT elevated/decreased despite the presence of anemia indicates bone marrow failure Peripheral Blood Smear (PBS) → Gives you the morphology or type of the anemia that can help determine the etiology of anemia Red Cell Distribution Width: 11.5-14.5 → Determines the presence of: ▪ Anisocytosis → variability in RBC size ▪ Poikilocytosis → variability in RBC shape → Higher value = more variability in size and shape of the red cell RED BLOOD CELL INDICES Tests to determine morphology → After a diagnosis of anemia by Hb and Hct, the next step is to determine RBC morphology (i.e., size and color) → Best to use: MCV and MCHC Figure 5. Pallor in conjunctiva and mouth (left) [Lecture PPT] Mean Corpuscular Volume (MCV) → Determines size PATHOLOGY Diseases of RBC & Bleeding Disorders PAGE 3 of 14 PATHOLOGY | LE 2 Diseases of RBC & Bleeding Disorders I | Araceli P. Jacoba → Hct/RBC count x 100 Caused by red cell disorders that affect the hemoglobin Mean Corpuscular Hemoglobin Concentration (MCHC) → Heme/Iron problems: → Determines color ▪ Iron deficiency anemia: deficiency in iron in Hb → Hb/ Hct x 100 ▪ Anemia of Chronic Disease: failure to release iron → Correlates with hemoglobin content from stores and failure to absorb iron from the gut Mean Corpuscular Hemoglobin (MCH) (cannot utilize iron) → Hb/ RBC count x 10 ▪ Sideroblastic Anemia: failure to incorporate iron in → Correlate value that follows the increase or decrease in Hb either MCV or MCHC → Globin problem: ❗️ Manifestation of anemia mainly depends on its etiology MCV and MCHC are best used in determining RBC ▪ Thalassemia: deficient or absent globin morphology ❗️ HYPERCHROMIC, MACROCYTIC ANEMIA Increased MCV, MCH and normal MCHC Defect in DNA synthesis Table 2. Normal Laboratory Findings Cobalamin (Vitamin B12) and Folic Acid (Vitamin B9) Male Female deficiencies → Megaloblastic Anemia Hemoglobin 13-16 g/dl 12-14 g/dl → 2 nutritional requirements in DNA synthesis Hematocrit 39-48% 33-42% Pernicious Anemia Reticulocyte count 0.5-1.5% → Failure to absorb Vitamin B12 Peripheral Blood Normochromic, normocytic Alcoholism and Liver Disease Smear → Less common causes of enlargement of RBCs but lead RBC Distribution 11.5-14.5 to non-megaloblastic types of anemia Width Table 3. Red Blood Cell Indices RBC Indices Normal Values Interpretations MCV 80-94fL (size) 94 - macrocytic MCHC 32-36 mg/dL 36 - hyperchromic MCH 25-34 pg Correlate value: If either MCV or MCHC is increased Figure 9. PBS Center: normocytic and normochromic; Left: or decreased, MCH Microcytic red cells (notice small size compared to follows lymphocyte); Right: Hypochromic red cells notice wide central the change pallor greater than 1/3 of red cell diameter [Lecture PPT] PERIPHERAL BLOOD SMEAR ❗️ Can also provide the morphology of the red blood cell NORMOCHROMIC, NORMOCYTIC ANEMIA Size is determined by comparing the RBC with the Normal MCV, MCHC and MCH smallest lymphocyte in the smear Included ALL other types of anemia not stated above → Normocytic: same size or only slightly smaller than the → Example: Hemolytic Anemia smallest lymphocyte → Microcytic: significantly smaller than the smallest lymphocyte CAUSES OF ANEMIA → Macrocytic: larger than smallest lymphocyte Blood loss Color is determined by the central pallor of the RBC → Losing blood from the intravascular space → Normochromic: 1⁄3 the diameter of the red blood cell → Can be acute or chronic → Hypochromic: greater than 1⁄3 ACUTE BLOOD LOSS → Hyperchromic: small or almost lost Normocytic, normochromic → Loss of large amount of blood in a short period of time (1000 cc within 10-15 mins) ▪ i.e. hemorrhage from motor vehicular accidents with gaping injury → Effects are mainly due to the loss of intravascular volume that can lead to CV collapse with hypotension and shock → Physiologic changes in blood if patient survives Figure 8. Comparison of RBC with lymphocyte on PBS[Lecture accident: PPT] ▪ Shift of interstitial fluid to intravascular space → CLASSIFICATION ACCORDING TO MORPHOLOGY aggravating ↓RBC and anemia ▪ ↓BP → mobilize granulocytes from bone marrow pool ❗️DecreasedHYPOCHROMIC, MICROCYTIC ANEMIA MCV, MCHC, and MCH leads to leukocytosis followed by thrombocytosis (immediately after injury) PATHOLOGY Diseases of RBC & Bleeding Disorders PAGE 4 of 14 PATHOLOGY | LE 2 Diseases of RBC & Bleeding Disorders I | Araceli P. Jacoba ▪ ↓O2 after injury stimulates the kidney to produce ▪ Increased Hb catabolism increases iron release and EPO which stimulates BFU-E → reticulocyte (occurs storage resulting in hemosiderosis, and increased 3-5 days after injury) storage of iron in sideroblasts and other tissues − Erythrogenesis takes this long after stimulation ▪ ↑hemosiderin → Summary of response to injury: Leukocytosis > Elevated Lactate Dehydrogenase (LDH) Thrombocytosis > reticulocytosis occurs after 3-5 days → Abundant enzyme in red cells CHRONIC BLOOD LOSS → Elevates in serum once red cell lyse accumulation of the products of Hb catabolism Hypochromic/microcytic Occult/ undetected (hidden) loss of blood that lead to loss INTRAVASCULAR HEMOLYSIS of iron or iron deficiency which is not replaced despite Occurs within the blood vessel chronic loses Once an RBC is lysed within the blood vessel, the Examples: malignancies (common in elderlies) following events occur: HEMOLYSIS (INCREASED RATE OF DESTRUCTION) → Hb is released from the blood →Hb attaches to haptoglobin for transport to the RES → final degradation The shortened lifespan of RBCs (