Hemolytic Anemia Part II FJ Albert, DO, DTM&H Hospital Medicine Lexington Medical Center West Columbia, SC Associate Professor Clinical Internal Medicine Edward Via College of Osteopathic Medicine Carolinas Campus

Disseminated Intravascular Coagulation (DIC) A systemic process producing BOTH thrombosis and hemorrhage Seen in sepsis, trauma, or malignancy

Disseminated Intravascular Coagulation Diagnosis Suspect if clinical picture consistent with DIC Thrombocytopenia Low plasma fibrinogen level Elevated plasma D-dimer Elevated Fibrin Degradation Products (FDP) Microangiopathic abnormalities on blood smear

DIC Treatment Most importantly, treat the underlying disease causing the DIC Commonly sepsis Hemodynamic support Bleeding patients with platelet count <50,000 – Platelet transfusion (Six pack will increase platelet count approximately 30,000) Bleeding patient with fibrinogen level <50 mg/dL or elevated PT/INR – Cryoprecipitate replaces fibrinogen (Goal >100mg/dL) – FFP reverses PT/INR elevation

DIC Treatment Treatment with intravenous heparin generally limited to chronic DIC with predominant thrombotic picture – Migratory thrombophlebitis (Trousseau’s sign) – Acral ischemia (distal extremities)

DMC

TLC

DIC

Malaria Overview “Mal” “aria” (“bad air”) Most cases, by far, occur in Africa Most fatal cases involve children in sub-Saharan Africa (Plasmodium falciparum) World wide distribution, however – Disease of poverty

Malaria Epidemiology

Malaria Overview Etiology is a protozoan parasite of the Plasmodium species Four main types – Plasmodium falciparum – Plasmodium vivax – Plasmodium ovale – Plasmodium malariae Vector is the Anopheles (female) mosquito Transmitted by blood Incubation for all species approximately 2 weeks – P. vivax and P. ovale can also manifest many months later Diagnosis typically by blood smear

Sir Ronald Ross Nobel Prize for Medicine 1902

Sir Patrick Manson

Musculoskeletal Malleolus Cervical Trachea Feet

Malaria Symptoms Fever Chills Headache Cough Vomiting Myalgias Fatigue

Malaria Signs Anemia (hemolytic) Splenomegaly Metabolic acidosis Hypoglycemia Renal failure Liver failure Hypotension Delirium (cerebral malaria)

Malaria Life Cycle (1) Anopheline (female) mosquito transmits infection (primarily bites at night) (2) Sporozoites in mosquito saliva infect human host (3) Sporozoites disappear from blood in approximately 8 hours (4) “Successful” sporozoites enter liver cells within 30 minutes

Malaria Life Cycle (5) Sporozoites divide asexually within liver cells and form into shizonts, while SOME sporozoites become dormant as hypnozoites within the liver  hypnozoites specific to P. vivax and P. ovale  schizonts=“vacuoles separate from hepatocyte cytoplasm, containing tens of thousands of merozoites”

Malaria Life Cycle (6) When mature, schizont ruptures, releases merozoites into bloodstream, and infect RBCs (7) Some merozoites infect other RBCs (i.e. hemolytic anemia), while others develop into gametocytes via sexual development (8) Gametocytes taken up by a mosquito blood meal  stomach/gut  salivary glands  bites and reinfects another human host

Malaria Life Cycle

P. Falciparum P. Vivax

Malaria Plasmodium vivax rare in West Africa Lack of Duffy antigen Parasite cannot adhere to RBCS that lack Duffy antigen

Malaria Prevention and Treatment Taking prophylaxis PROPERLY prior to arrival as well as throughout stay within an endemic area (NO 100% protection) DEET-containing insecticides Covered clothing Using permethrin treated bed nets Primaquine after leaving endemic area – Hypnozoite phase of P. vivax/P. ovale

Quinine First discovered drug to treat P. falciparum malaria (17 th century) Occurs naturally in bark of cinchona tree, native to Andes Mountains of Peru and Bolvia – “Suppressed fevers” when bark ingested Discovered by Quechua Indians and brought to Europe by Missionary Jesuits – First treated case in Europe in 1631 (Rome, Italy)

Quinine Bitter taste Drug of choice for malaria treatment from 1600s until 1940s Chloroquine replaced quinine as drug of choice in the 1940s (more tolerable) Several other medication classes have since been discovered for prophylaxis and treatment of malaria

Quinine Used to treat Systemic Lupus Erythematosus (SLE) “Nocturnal muscle cramp remedy” – Muscle relaxant – Use now much less common (FDA warning discouraging use) Minute quantities remain in tonic water

Medication Options for Malaria Chemoprophylaxis (initiated prior to arrival and continued throughout stay in an endemic area) – Chloroquine – Mefloquine – Doxycycline – Atovaquone-Proguanil

Medication Options for Malaria Options for treatment of suspected or confirmed disease – Quinine – Chloroquine – Amodiaquine – Sulfadoxine-Pyrimethamine (Fansidar) – Atovaquone-Proquanil (Malarone) – Artemisinin class of drugs Costly Black Market

Henoch-Schonlein Purpura (HSP) Most common systemic vasculitis of childhood Usually occurs ages 3-15 – Peak at ages 4-6 Approximately 10 pecent of cases are adults

Henoch-Schonlein Purpura (HSP) Clinical Manifestations – Palpable purpura, without thrombocytopenia or coagulopathy – Arthralgias/arthritis – Abdominal pain – Renal disease

Henoch-Schonlein Purpura (HSP) Underlying cause is not known Presumed immune-mediated vasculitis triggered by antigens – Infections (viral or bacterial) or immunizations No diagnostic tests exist

Palpable Purpura in HSP

Henoch-Schonlein Purpura (HSP) Outpatient treatment – Oral hydration – Bed rest – Symptomatic relief of abdominal and joint pain Inpatient treatment – IVF – NSAIDS (e.g. naproxen) – Steroids (oral or IV) if NSAIDS not effective

Henoch-Schonlein Purpura (HSP) Excellent prognosis, overall Small percentage develop long term renal disease Long term renal disease more common in adults with HSP