Ch 29- Alterations of hematological fxn

Disseminated Intravascular Coagulation (DIC)

• Complex, acquired clinical syndrome
• DIC involves widespread coagulation activation, resulting in fibrin clot formation in small to medium vessels
• Multi-organ failure occurs when blood flow to organs becomes blocked
• Platelets and clotting factors are consumed because of excess clotting
• Severe bleeding occurs despite widespread clots

Clinical Course

• Clinical course determined by intensity of stimulus, comorbidities, and host response
• The severity can range from localized to one specific organ or generalized involving multiple organs
• An acute, severe, life-threatening process can occur, with massive hemorrhage and thrombosis
• A chronic, low-grade condition characterized by subacute hemorrhage and diffuse microcirculatory thrombosis can occur

Associated Clinical Conditions

• Wide range of well-defined conditions capable of activating the clotting cascade can occur:
• Arterial hypotension frequently accompanies shock
• Hypoxemia
• Acidemia
• Stasis of capillary blood flow

Etiology

• Sepsis is the most common condition linked to DIC
• Gram-negative microorganisms, fungi, protozoa (malaria), and viruses (influenza, herpes) damage vascular endothelium, precipitating DIC
• Gram-toxins are a primary cause of endothelial damage and can cause DIC in up to 50% of individuals with gram-sepsis
• 10-20% of individuals with metastatic cancer or acute leukemia
• Direct tissue damage from ischemia, necrosis, surgical manipulation, or crushing injury leads to tissue factor (TF) release by the endothelium
• Severe brain trauma induces DIC in two-thirds of individuals with a systemic inflammatory response to trauma
• Complications of pregnancy ranging from 50% placental abruptions to less than 10% severe preeclampsia
• Blood transfusions dilute clotting factors and circulating antithrombins
• Hemolytic blood transfusion reactions damage the endothelium via complement-mediated reactions

Pathophysiology

• Abnormally widespread and ongoing clotting activation results in excessive tissue factor exposure
• Widespread damage to the vascular endothelium exposes subendothelial tissue factor
• Several types of cells express tissue factor after stimulation or constitutively
• Endotoxin triggers the release of multiple cytokines which then activate the endothelium to initiate thrombi development
• TNFα, interleukins IL-1, IL-6, IL-8, and platelet-activating factor (PAF) are proinflammatory cytokines responsible for clinical signs and symptoms associated with sepsis.
• Tissue factor is released directly into the bloodstream from circulating white blood cells (WBCs) from monocyte/endotoxin interaction
• Tissue factor binds to clotting factor VII, prothrombin converts to thrombin, and fibrin clots form, initiating DIC

Clotting and Anticoagulants in DIC

• The clotting system is activated extensively
• The predominant natural anticoagulants are greatly diminished that includes tissue factor inhibitor, antithrombin III, and protein C and diminished fibrinolysis
• DIC can be precipitated by direct proteolytic activation of factor X
• Clotting system activation decreases levels of Tissue Factor Inhibitor, Antithrombin III [AT-III], PROTIEN C

DIC Process

• Activation of clotting consumption of clotting factors and platelets continues with persistent thrombin production
• Thrombomodulin expression decreases due to cytokine-mediated expression on the endothelial cell surface

Clinical Manifestations

• Hemorrhage or thrombosis cause the most symptoms
• Acute DIC presents with hemorrhaging, such as oozing from venipuncture sites, arterial lines, and surgical wounds, or ecchymotic lesions (purpura, petechiae) and hematomas
• Bleeding includes the eyes (sclera and conjunctiva), the nose (epistaxis), and the gums
• Most individuals exhibit bleeding of three or more unrelated sights in any combination
• Shock of variable intensity may also be observed, which is out of proportion of amount of blood lost
• Hemorrhaging into closed compartments of the body can precede the development of shock

Organs Susceptible to Microvascular Thrombosis

• Cardiovascular
• Pulmonary
• Central Venous
• Renal
• Hepatic

Rapid Diagnosis and Indicators of Multisystem Failure

• Rapid and accurate clinical diagnosis helps prevent further progression
• Indicators of multisystem failure include:
• LOC changes, behavior, and mentation
• Confusion
• Seizure activity
• Oliguria
• Hematuria
• Hypoxia
• Hypotension
• Hemoptysis
• Chest pain
• Tachycardia
• Symmetric cyanosis of fingers and toes, and occasionally nose and breasts, which is often indicative or microvascular thrombosis.
• Can progress to infarction and gangrene, as well as jaundice

Chronic or Low-Grade DIC

• Manifests as subacute bleeding and diffuse thrombosis, which is compensated or non-overt
• Characterized by an increased turnover and decreased survival time of the components of hemostasis, the platelets and clotting factors
• Diffuse or localized thrombosis may develop

Evaluation

• Diagnosis relies on clinical symptoms
• Diagnosis relies on a combination of lab tests
• Individuals must exhibit a clinical condition related to DIC association
• Thrombocytopenia confirms, or a rapidly decreasing platelet count on repeated testing
• Prolongation in clotting times and indication of fibrin degradation products

Thrombocytopenia for DIC

• Platelet count <100,000
• Progressive decrease in platelet counts
• Platelet tests are sensitive to DIC in patients

Testing

• D-dimer detects fibrin degradation
• ELISA’s are used to detect thrombin activity

Diagnosis Criteria

• Systemic thrombohemorrhagic disorders with laboratory evidence of:
• Clotting Activation
• Fibrinolytic Activation
• Coagulation Inhibitor Consumption
• Biochemical evidence of end-organ damage or failure

Treatment

• Treatment is directed toward:
• Eliminating underlying pathology
• Controlling ongoing thrombosis
• Maintaining organ function

Medical Treatment

• Heparin has been used for thrombosis control
• Heparin's use is controversial because its mechanism of action is binding to and activating AT III
• AT III is deficient in many types of DIC
• Replacement therapy can restore coagulation factor balance, by replacing deficient coagulation factors and platelets
• Platelets, fresh frozen plasma and cryoprecipitate can be used during replacement
• Anti-fibrinolytic drugs are used in treatment but are limited to instances of life-threatening bleeding
• Organ function maintenance is achieved by fluid replacement. This sustains blood volume and maintains optimal perfusion

Macrocytic-Normochromic Anemia

• Pernicious Anemia (B12) and folate deficiency anemia cause this
• Macrocytic (megaloblastic) anemias leads to large stem cells (megaloblasts) in the marrow
• Erythrocytes in maturity are large in size (macrocytes), thickness, and volume

Megaloblastic Anemias

• Defective erythrocyte DNA synthesis occurs
• Defective DNA synthesis leads to deficiencies of vitamin B12 and folate, coenzymes needed for nuclear maturation and DNA synthesis
• Normal hemoglobin content occurs in a normochromic state

Defective Erythrocyte DNA Synthesis

• B12 deficiency (cobalamin) or folate (folic acids) impairs a number of coenzymes needed for nuclear maturation and DNA synthesis
• Defective erythrocytes die prematurely which causes anemia
• Eryptosis describes the premature death of damaged erythrocytes

Situations Relating to Eryptosis

• Deficiencies of iron, chronic diseases (DM, renal), genetic diseases, and myelodysplastic syndrome
• Anemia
• Infections (malaria)
• Erythrocyte life span, decreased by 50%

Defective DNA Synthesis Signs

• Defective DNA synthesis causes RBC growth and development at unequal rates
• DNA synthesis and cell division are blocked or delayed, but RNA and Hgb synthesis proceed normally
• Asynchronous development causes an overproduction of hemoglobin and a larger erythrocyte with a smaller nucleus

Pernicious Anemia (PA)

• Vitamin B12 deficiency is the cause
• Pernicious Anemia is often associated with end stage of type A chronic atrophic (congenital or autoimmune gastritis which destructs parietal or zymogenic cells
• Pernicious means injurious/destructive
• Pernicious Anemia represents an once fatal condition

Principal Disorder in PA

• Principal disorder in PA consists of the absence of the transporter intrinsic factor (IF)
• B12 deficiency is essential for nuclear maturation and DNA synthesis, and proper transporter function
• Intrinsic Factor is secreted by gastric parietal cells and complexes with dietary B12 in the small intestine
• B12-Intrinsic Factor binds to cell surface receptors in the ileum and transports across the intestinal mucosa
• Autoantibodies are directed against gastric parietal cells
• Autoantibodies are formed against gastric H+-K+-ATPase (major protein constituent of parietal cell membranes).
• May be a result of H. pylori

Demographic and Symptoms for Pernicious Anemia

• Affects individuals > 30, and those of North European decent, primarily those of Scandinavian, English, and Irish descent
• PA is less common in Greek or Italian heritage individuals
• PA is being more reported in blacks and Hispanics. Females prone to develop with black females having an earlier onset
• Develops slowly over 20 to 30 years, median age at diagnosis is 60 years of age
• Early symptoms are normally ignored, they're vague: infections, mood swings, GI, cardiac, and kidney ailments
• Hemoglobin drops
• Paresthesia involves feet/fingers due to myelin degeneration in the spinal cord
• Lemon yellow skin
• Position loss and vibration, ataxia, with posterior and lateral columns affected and pose serious never irreversible threats
• Cerbrum relates to depressive disorders, Alzheimer disease increase and thyroiditis

Pernicious Anemia Diagnosis and Complications

• Blood test, bone marrow aspiration, serologic studies, gastric biopsy, and clinical manifestations are diagnostic
• Schilling test replaces serologic studies and is no longer a standard method for laboratories
• Gastric biopsy determines achlorhydria
• Untreated PA leads to heart failure

Vitamin B12 Actions

• B12 is essential for maturation and DNA synthesis through erythrocytes
• Pernicious Anemia is treated with replacing Vitamin B12
• Correcting a deficiency with vitamin B12 initially involves weekly injections and then monthly injections for life because pernicious anemia is incurable and requires lifelong treatment
• Rising reticulocyte count is the determining factor

Deficiencies in B12

• Deficiencies in B12 are essential for nuclear maintenance and DNA synthesis
• Pernicious Anemia is caused by deficiencies in B12
• Associated through Northern Europeans in age of 30
• Type A Gastritis
• Absence of B12 transporter intrinsic factor creates deficiency

Folate

• Folate is vitamin B that is a coenzyme required for synthesis of thymine, conversions, blood components, absorption and function
• Needed for homocysteine to to methionine conversion
• Stored in the liver and absorbed in the digestive tract

Folate Deficiency

• Folate deficiency impairs DNA synthesis in megaoblastic cells
• Late erythroblast results in immune response, and may result from deficiency
• Folate protects against anemia and is in several everyday processes

Complications via Folate Deficiencies

• Homocysteine isn't reduced without Folate and raises likelyhood of Coronary Artery Disease
• Causes risk towards colorectal cancer
  • Not now, supplements are decreasing numbers

Etiology

• Often affects those in poverty, those with other conditions or alcoholism. It's less common than B-12 deficiency
• Fad diets can hinder absorption of iron

Identification

• May see malnourishment as they're often paired
• May see GI irritation, neuro inflammation or neural problems

Treatment

• Measure levels
• Reduce symptoms with treatments
• After deficiency, maintain healthy level and should subside

Microcytic-Hypochromic Anemias

• Iron Deficiency & Sideroblastic
• Abnormally low hemoglobin and size are key characteristics to the two deficiencies

Iron Deficiency

• Ineffective function of multiple organ systems is key for classifying it to low size
• Results from iron and erythropoiesis abnormalities

Factors in iron and Blood production

• Meds
• Malfunctions
• Diet

Stages

• Depleted
• Diminished
• Deficient

Iron Deficiency Signs

• Low volume
• Not as much synthesis or production to where multiple organ systems malfunction

High Risk Deficient Groups

• Female
• Pregnant
• Low Economic Status

Manifestations

• Low energy
• Cognitive fatigue
• SoB (Shortness of Breath)

Symptoms

• Decreased organ function
• Low iron
• Anemia

Normocytic-Normochromic Anemia

• A result of blood or organ systems is the resulting problem, for which can lead to a treatment goal
• The Anemia has some basic function loss

Anemia Diagnoses

• H/H
• Bone Scan

Hemolytic Anemia

• Results from immune issues
• Often autoimmune

Drug induced Anemia

• Happens for several reasons
• Transfusions are one way to help

RBC Traits

• Production
• Destruction (crisis may result)

Complications of Hemolytic Anemia

• Normo and Hypo conditions can result from it
• Often a progressive disease

Polycythemia

• RBC creation in multiple ways is related
• High altitude

Polycythemia vera

• Over the top production (Overload)
• Viscosity high which leads to clotting

Hematochromosis

• Genetic defects cause this, is progressive
• Iron is retained and causes damage long-term to many systems

Mononucleosis

• Patho
• Transmitted easily
• Lymphocytes increase

Manifestations

• Immune system responses cause symptoms, swollen glands, achiness

Complications

• It is manageable

Leukemia

• A proliferation is what is classified in a general statement
• Marrow creates many cells

Diagnoses

• Marrow checks determine amount of cells
• Symptoms start to appear, this often causes death

Lymphomas

• Hodgkins
  • Progressive diseases have characteristics
  • Infections
  • Nodal spread

No Hodgkins

• Genetic mutations cause this
• Pain-free swelling is often a symptom

LL Lmphoblastic lymphomas

• Can be acute
• Genetic abnormalities contribute

LL Manifestations

• Mass growth
• Mediacl mass (often a T-Cell, often diagnosed in the Thymus)

Burkitt Lymphomas

• Cells grow quickly and cause genetic mutations
• Can result from EBV transmissions

Burkitt Complications

• Affects systems depending on specific disease and type
• Treatment depends on disease and severity of conditions